Lupus in the Lung

1. Lupus in the Lung

2. Pulmonary manifestations in SLE By: HaidyMohamed Ass. Lecturer of Rheumatology and rehabilitation Supervised by: Prof. Gihan Omar Professor of Rheumatology and Rehabilitation Minia University • Prof. Ahmed Abdel-Nasser • Professor of Rheumatology and Rehabilitation • Minia University

3. Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease that may involve many different organs and display a variable clinical course. • The diagnosis of SLE is based on characteristic clinical findings of the skin, joints, kidneys, and the central nervous system, as well as on serological parameters such as antinuclear antibodies (ANA), in particular antibodies to dsDNA.

4. Although SLE has the potential to affect any organ, the lungs are commonly involved later in the course of the disease. • Lung disorders are classified as primary (due to lupus) and secondary to other conditions such as infection and drug toxicity.

5. Respiratory involvement in patients with lupus: • Primary lung disorders • Pleural involvement • Pleurisy • Pleural effusion • 2) Parenchymal involvement • Acute lupus pneumonitis • Chronic interstitial lung disease

6. 3) Vascular involvement • Non-thromboembolic disease • Diffuse alveolar haemorrhage (DAH) • Pulmonary arterial hypertension (PH) • Acute reversible hypoxaemia (ARH) • Thromboembolic disease (DVT, PE) • 4) Diaphragmatic involvement (SLS) • 5) Airways involvement

7. Associated lung disorders • 1) Adult respiratory distress syndrome (ARDS) • 2) Pulmonary drug toxicity • 3) Respiratory infections • 4) Sarcoidosis • 5) Cancer - Lung cancer

8. Primary lung disorders

9. Pleural involvement • Pleurisy • Pleural effusion

10. Pleural Disease • Approximately 30% to 50% of patients with SLE will develop symptomatic pleural inflammation over the course of their disease, and in 5% to 10% of patients, pleuritis is the initial manifestation. • The typical presentation of pleural involvement in SLE is sharp chest pain with deep breath (pleurisy). • Pleural effusions in SLE tend to be bilateral but small, and may not be evident on radiographic imaging.

11. Characteristics of pleural fluid in sle:

12. Pleural disease in SLE typically responds well to non-steroidal anti-inflammatory drugs or low-dose corticosteroids. • Small asymptomatic effusions usually resolve spontaneously without therapy. • Occasionally, moderate to high dose corticosteroids are needed for resolution of the pleural inflammation and rarely other immunosuppressantsare required to control refractory or recurrent pleuritis.

13. 2)Parenchymal involvement • Acute lupus pneumonitis • Chronic interstitial lung disease

14. Parenchymal Lung Disease • Acute lupus pneumonitis (ALP) • Albeit rare, occurring in 1% to 12% of patients, acute lupus pneumonitis is one of the most serious pulmonary complications of SLE. • Patients usually present with fever, cough, pleurisy, dyspnea with hypoxia, and sometimes hemoptysis. • The most immediate concern for patients with suspected lupus pneumonitis is to exclude the presence of a pulmonary infection, because these two diseases have similar presentations but very different treatments.

15. In ALP, • There are negative sputum and blood cultures (no causative organism can be isolated) with positive ANA and low complement levels in pleural fluid analysis. • Broncho-alveolar lavage (BAL) reveals increased cellularity with activated polymorphonuclear leukocytes. • Chest radiography shows pleural effusions and alveolar pulmonary infiltrates, particularly in the lower lung fields.

16. The mainstay of acute lupus pneumonitis treatment is systemic corticosteroids (prednisone 1–1.5 mg/kg/d in divided doses). • If the response to oral corticosteroids is not adequate within 72 hours or the patient has marked tachypnea, hypoxemia, or suspected diffuse alveolar hemorrhage, treatment should include intravenous pulse corticosteroids (ie, 1 g methylprednisolone per day for 3 days). In addition, immunosuppressants such as cyclophosphamide should be considered.

17. 2) Chronic interstitial lung disease • Chronic interstitial lung disease (ILD), also called fibrotic lupus pneumonitis, is seen in 3% to 13% of patients with SLE, primarily in patients with long-standing disease. • ILD often develops insidiously, with gradually worsening nonproductive cough, dyspnea on exertion, and recurrent pleurisy, but can also appear following an episode of acute lupus pneumonitis.

18. Similar to idiopathic pulmonary fibrosis, examination reveals bibasilar inspiratory pulmonary crackles. Lung function tests show a restrictive pattern with reduced lung volumes (FEV1st and FVC), normal FEV1st/FVC ratio and reduced diffusing capacity for carbon monoxide (DLCO).

19. Chest radiographs may be normal or reveal bibasilar irregular linear opacities early in the course. More diffuse infiltrates, pleural disease, or honeycombing appear later in the course. • High resolution computed tomography (HRCT) is helpful to evaluate for the ground-glass appearance associated with cellular infiltration or fibrosis and for the reticular pattern associated with fibrotic disease.

20. The histopathologic pattern of chronic ILD in SLE is mostly NSIP including alveolar septal thickening, interstitial fibrosis, lymphocytic infiltrates, alveolar septal immune deposits, and type II pneumocyte hyperplasia, however other patterns (UIP, LIP,OP and DIP) can also occur.

21. Oral corticosteroids (prednisone 30 mg/d for at least 2- 4 weeks) are a reasonable first line therapy for symptomatic patients. • Regarding immunosuppressants, the optimal choice for SLE-related ILD is uncertain, but cyclophosphamide, azathioprine, and mycophenolate have all been tried in situations of inadequate response to corticosteroids.

22. 3) Vascular lung disease • Non thromboembolic diseases • Diffuse alveolar hemorrhage • Pulmonary hypertension • Acute reversible hypoxemia (ARH)

23. Diffuse alveolar hemorrhage • Diffuse alveolar hemorrhage (DAH) is a rare and potentially fatal complication of SLE. • Patients with DAH present acutely ill, often with dyspnea, cough, hemoptysis, and sometimes fever. • DAH typically presents in patients with established SLE, often in the setting of active lupus nephritis or other active organ involvement.

24. The hematocrit value of a patient with active DAH will usually drop quickly with a significantly elevated DLCO in PFT. • BAL is useful in excluding infection and the presence of persistently bloody fluid with hemosiderin-laden macrophages helps to confirm DAH.

25. It is also important to look for other forms of pulmonary vasculitis, such as antineutrophil cytoplasmic antibody–associated vasculitis, and screen for coagulopathies and thrombotic thrombocytopenic purpura as part of the evaluation. • Concomitant cyclophosphamide given with the high-dose corticosteroids improves the prognosis greatly. • DAH is also one of the few indications for plasmapheresis in SLE.

26. 2) Pulmonary hypertension • Symptomatic pulmonary hypertension (PH) is considered a rare complication of SLE, and is more often seen with SLE overlaps with other connective tissue diseases, particularly scleroderma or mixed connective tissue disease.

27. Symptoms of SLE-PH most commonly include dyspnea, chest pain, nonproductive cough, and fatigue. • Patients may also develop peripheral edema and other findings consistent with PH, including jugular venous distension, fixed S2 splitting, murmurs of tricuspid regurgitation or pulmonic insufficiency, and hepatomegaly with ascites.

28. The first-line of diagnostic testing for patients with suspected SLE-PH involves obtaining a Doppler echocardiogram to look for elevations in estimated pulmonary artery pressure and resistance and/or tricuspid valve insufficiency. • Finding an isolated diffusion defect on lung function testing may be an early predictor of SLE-PH. • Right heart catheterization (RHC) is required to confirm the diagnosis and gauge the severity of PH.

29. Potential therapies include: • Vasodilators: • Endothelin receptor antagonists (bosentan, ambrisentan). • Phosphodiesterase-5 inhibitors (Sildenafil, tadalafil). • Prostanoids: (Epoprostenol, iloprost and Treprostinil).

30. Oxygen therapy (especially in patients live at high altitude or have sleep apnea, however some patients may eventually require continuous oxygen therapy) • Anticoagulation (to prevent formation of blood clots within the pulmonary arteries, Warfarin is given with regular monitoring of the INR). • Treatment of the underlying SLE with immunosuppressants may provide added benefit when combined with PAH-specific therapy.

31. 3) Acute reversible hypoxemia (ARH) • Unexplained hypoxemia by arterial blood gas with associated diffusion abnormalities and without obvious parenchymal lung disease has been described among hospitalized patients with SLE.

32. Although traditional workup was unrevealing regarding etiology of the reversible hypoxemia, plasma C3a levels were markedly elevated, suggesting pulmonary leuko-aggregation and complement activation within pulmonary capillaries.

33. Gas exchange improved within 72 hours of initiating corticosteroid therapy. • The majority of published cases report good responses to corticosteroids, either alone or in combination with aspirin.

34. Thromboembolic disease (DVT, PE) • Deep venous thrombosis (DVT) with or without pulmonary embolism (PE) have been identified in approximately 9% of the patients with SLE and are commonly associated with activity of the disease. • The presence of anti-phospholipid antibodies increases the risk of thromboembolic events to 35–42%.

35. Pulmonary embolism (PE) in lupus patients usually presents with sudden onset of pleuritic chest pain and dyspnea. • Pulmonary angiography is the gold standard to confirm the diagnosis of PE. However, most cases are documented by V/Q scintigraphy or spiral CT scan.

36. Immunosuppressive therapy alone is rarely effective, and most patients are given chronic anticoagulation. • Prophylactic treatment with daily aspirin is often used in SLE patients with antiphospholipid antibodies but no history of a thrombotic event. • Patients with a known thrombotic event history should be treated with anticoagulation with heparin in the short term and warfarin in the long term, with a target international normalized ratio of at least 2 to 3.

37. 4) Diaphragmatic involvement • Shrinking lung syndrome

38. Diaphragmatic involvement • Shrinking lung syndrome • Shrinking lung syndrome (SLS) is a rare complication of SLE, estimated between 0.5% and 1.1% in the general lupus population. • The major symptom of SLS is progressive exertional dyspnea of variable severity, accompanied by pleuritic chest pain in three quarters of patients. • The recommended first-line procedures for diagnosis should include chest x-ray and thoracic HRCT, along with pulmonary and diaphragmatic function tests.

39. The most distinctive findings were elevated unilateral or bilateral hemi diaphragms with reduced lung volumes, a restrictive ventilatory defect in PFT with reduced TLC and DLCO in absence of parenchymal lung disease or vascular pathology on imaging techniques, and reduced MIP and MEP.

40. The evaluation of diaphragm dome motion by M-mode ultrasonography or dynamic contrast-enhanced lung MRI might be a useful second-line tool to reinforce clinical suspicion in cases of diagnostic difficulty.

41. There are no standardized guidelines for the treatment of SLS in SLE. According to the available experience, the majority of patients should be initially treated with medium or high doses of glucocorticoids. • An immunosuppressive agent (azathioprine or cyclophosphamide) should be used in conjunction with steroids if the patient failed to improve, and it is advisable from the beginning of the treatment in patients with severe clinical and functional decline.

42. The use of rituximab with or without concomitant immunosuppressive agent may be highly beneficial in restoring near-normal lung function.

43. 5) Airways involvement • Involvement of the upper airways occurs in about 0.3–30% of lupus patients and may range from laryngeal mucosal inflammation, mild ulcerations, cricoarytenoiditis, vocal cord paralysis and oedema to necrotizing vasculitis with airway obstruction. • Angio-oedema involving the upper airways is uncommon but may cause airway obstruction and require mechanical ventilation. It occurs during active disease and often follows symptoms of a respiratory tract infection.

44. Bronchial wall thickening and bronchiectasias on chest HRCT were detected in approximately 20% of lupus patients, but they are commonly clinically silent. • Abnormalities in PFTs (obstructive pattern with decreased FEV1st and FEV1st/FVC ratio) have been described in lupus patients, but severe airway obstruction is rare.

45. Few cases of bronchiolitis obliterans and cryptogenic organizing pneumonia associated with lupus have been described. • A variable response to steroids alone or in combination with cyclophosphamide has been reported.

46. Associated lung disorders

47. Associated lung disorders • Acute respiratory distress syndrome • Acute respiratory distress syndrome (ARDS), as defined by international consensus, can occur from acute lupus pneumonitis, DAH, or pulmonary infection. • ARDS has been most often described in patients with SLE in association with bacteremia or sepsis with gram-negative bacilli.

48. Treatment of ARDS is supportive, including: • Mechanical ventilation. • Prevention of stress ulcers. • Prevention of venous thromboembolism. • Nutritional support.

49. Mechanical Ventilation: • Most patients with ARDS need sedation, intubation, and ventilation while the underlying injury is treated. • Any ventilator mode may be used, Settings are adjusted to maintain an oxygen saturation of 88 to 95%. • Pharmacological Therapies: • The use of corticosteroids is controversial. • Cohort studies tend to support early use of corticosteroids for decreasing the number of days on a ventilator.

50. In addition to ventilatory measures, patients with ARDS should receive low-molecular-weight heparin (40 mg of enoxaparin subcutaneously per day) to prevent venous thromboembolism. • Patients should also be on stress ulcer prophylaxis with an agent such as sucralfate, ranitidine or omeprazole. • Finally, patients should receive nutritional support within 24 to 48 hours of admission to the ICU.