Pulmonary Pulmonary Manifestations of Manifestations of Systemic LupusSystemic Lupus

By Wafaa Laimon

Assistant Lecturer of PediatricsMUCH

* Systemic lupus erythematosus (SLE) is a rare complex autoimmune disease with a multisystem involvement. (Torre et al, 2011)

* SLE may affect all components of the respiratory system; pleura, alveoli, airway, interstitium and respiratory muscles. (Shen et al, 2005)

* Pulmonary manifestations varies between pleuritic chest pain to life threatening pulmonary hemorrhage.

* Respiratory affection is a part of SLE or secondary to its complications. (Lalani et al, 2004)

*Difficult to determine due to high rate of chest infections. (Bosch X et al, 2005)

*Dyspnea and exercise intolearnce in 40-75 % of adults with SLE . (Lalani et al, 2004)

*Lung involvement occurring in 80% of SLE patients at autopsy (mainly due to infections). (Pego-Reigosa et al, 2009)

*Rare in children with neither specific clinical findings nor pathognomonic radiological finding. (Kamen et al, 2010)

*In some literature, pulmonary involvement reach 5-67% of children with SLE

*Lung involvement in SLE is more common in males. (Kamen et al, 2010)

OUTLINES

Pulmonary embolism

Diffse alveolar hemorrage

Pulmonary hypertension

Chronic lupus pneumonitis

Shrinking lung syndrome

Acute reversal hypoxemia

Others

*Serositis (Pleuritis) is one of the diagnostic ACR (American College of Rheumatology) criteria for SLE.

*It occurs in 30-50% of patients with SLE. (Pines et al, 1985)

*Pleuritis is an initial manifestation in 2.5-3% of patients. (Sarwar A et al, 1999)

*It may be asymptomatic or present with chest pain and fever.

*Effusion is an initial presentation in 1-2 % of cases. (Wan KS, 2008)

*It occurs in 30 % of cases. (Dubois EL et al, 1964)

*Effusion is usually bilateral.

*It is usually small or moderate.

*Effusion is a mild exudate with elevated LDH, low C3 and may show LE cells. (Kushwaha R et al, 2008)

*Effusion is usually bilateral.

*It may be asymptomatic.

*It is usually small or moderate.

*Effusion shows low C3 with elevated LDH.

J Cytol. 2012 Jan-Mar; 29(1): 77–79.

Fate:*Effusion heals spontaneously without any residual damage.

*It may cause pleural thickening leading to chronic breathlessness.

Treatment:*Non-steroidal anti-inflammatory drugs (2-4 w).

*Low dose steroids 5-10 mg/day (4-6 w).

*Refractory or recurrent 1mg/kg/d (4-6 w),immunosuppressive drugs and pleurodesis.

Children with

* Leucopenia

* Low C3

* Positive antidsDNA

More likely to have pulmonary pleural diseases

*It occurs in 1-12 % of cases. (Cheema GS et al, 2000)

*It simulates infectious pneumonia.

*It may be initial presentation.(Challenging diagnosis).

*An abnormal interstitial pattern of ground glass appearance or honeycomb appearance is seen on HRCT chest.

Treatment:*High doses of corticosteroids 1-1.5 mg/kg/day orally (6 weeks).

*Pulse of methylprednisolone 1 gm/day for 3 days intravenously with (IV) with Cyclophosphamide IV followed by oral steroids should be considered.

*Rituximab.

*It affects 3-13 % of patients.

*It is characterized by gradually progressive exertional dyspnea, dry cough and recurrent episodes of pleurisy.

*Investigations:

1. Chest Xrays:

*Normal

*Reticulonodular shadows

*Honey Comb appearance

2. HRCT: is needed to differntiate active from chronic lesions.

3. Pulmonary function tests: restrictive pattern.

4. Gallium 67 scan.

*Nonspecific interstitial pneumonia (NSIP).

*Usual interstitial pneumonia (UIP).

*Lymphocytic interstitial pneumonia (LIP).

Treatment:*Asymptomatic: no treatment.

*Symptomatic: steroids and immunosuppresive drugs.

*It is increase in mean pulmonary arterial pressure (mPAP) ≥25mmHg at rest, Pulmonary artery wedge pressure (PAWP), or left ventricular end diastolic pressure ≤15mmHg and increased pulmonary vascular resistance (PVR).(McLaughlin et al, 2009)

*Prevalence in SLE: 0.5% to 17.5%. (Arnaud, 2011)

Dhala et al, 2012

Dhala et al, 2012

(i) Female gender

(ii) Isolated reduction in diffusion

(iii) Raynaud phenomenon

(iv) Serositis

(v) Renal disease

(vi) Digital gangrene

(vii) Cutaneous vasculitis/livedo reticularis

(viii) Rheumatoid factor

(ix) Anti-U1 RNP

(x) Anticardiolipin antibodies

(xi) Antiendothelial cell antibodies

Treatment:

*Immunosuppressive and anti-inflammatory therapies, coupled with vasodilator therapy.

*It is due to pulmonary vasculitis.

*It is life threatening condition.

*Active nephritis and hypoalbuminemia is a major risk factor.

*Age: 15-45 years (Mean 30 years).

*Female:male ratio 6:1. (Kamen et al, 2010)

*It occurs in <2 to 5.4% in cohorts of lupus patients and accounts for 1.5 to 3.7% of hospital admission due to SLE. (Santiago-Casas et al,2009)

*It is characterized by “Classic triad” of hemoptysis, rapid fall in hemoglobin over 24–48 hours, and new alveolar or interstitial infiltrates.

* High titers of anti-dsDNA, hypocomplementemia, and anemia are frequently noted.

*Decrease in carbon monoxide (DLCO) is sensitive marker for active alveolar bleeding.

*Sequential bronchoalveolar lavage sample from the same location with increasing red blood cell count is diagnostic.

*In subacute cases: Presence of hemosiderin-laden macrophages from BAL fluid

*Pathological patterns:

1. Bland hemorrage.

2. Alveolar capillaritis.

3.Alveolar Damage.

Treatment*Pulses of methyl predinsolone.

*Cyclophosphamide

*Plasma pharesis

*?? B cell depletion therapy (Rituximab)

*Recombinant aVII (Novoseven)

It is characterized by:*Unexplained dyspnoea.

*Small lung volumes.

*Restrictive pattern on PFT in absence of ILD.

*Bilaterally elevated domes of diaphragm on chest X-rays.

*It is due to intercostal muscle weakness or diaphragmatic weakness resulting from an inflammatory myopathy or phrenic neuropathy.

Treatment*Pulses of methyl predinsolone.

*Cyclophosphamide

*Rituximab

*Theophyline

*Diaphragmatic plication

*It is not a specific lung problem of SLE.

*It is a complication of acute lupus pneumonitis,DAH or pulmonary infections.

*Gram negative sepsis is its commonst cause.

*More with antiphospholipid syndrome.

It can lead to:

*Pulmonary infarction

*Pulmonary hypertension

*Diffuse alveolar hemorrhage

*ARDS

Treatment: anticoagulant to keep INR 2:3

---If no history of thrombosis: antiplatelet (no evidence)

*It is unexplained hypoxia in the absence of parenchymal lung disease which responds to steroids within 72 hours

*Causes:

*Pulmonary leukoaggregation

*Complement activation

*Pulmonary capillaritis

*Upregulation of adhesion molecules like E-selectin, VCAM-1 and ICAM-1

*It is met in 30% of SLE patients.

*It can affect upper and lower airway.

*Marvellous response to inhaled and parentral steroids.

*Bronchoilitis Obliterans Organizing Pneumonia (BOOP):

characterized by the formation of fibrous tissue plugs within terminal bronchioles and alveolar ducts.

*Diagnosis: transbronchial lung biopsy.

*SLE may affect all components of the respiratory system.

*Clinical presentation varies between asymptomatic condition to life threatening state.

*Pleural affection is the commonst respiratory involvement in SLE.

*Pulmonary infiltration in SLE is not always infection.

*Pleural effusion in lupus patient has causes other than infection.

*Positive ANA in pleural fluid favors lupus activity rather than infection.

*Diffuse alveolar hemorrhage is characterized by “Classic triad” of hemoptysis, rapid fall in hemoglobin over 24–48 hours, and new alveolar or interstitial infiltrates.

*Pulmonary manifestations of SLE need further studies.

Thank You