Pleuropulmonary Disease Flashcards
Systemic Sclerosis “scleroderma”
- more lung disease than any other autoimmune connective tissue disease (collagen vascular disease)
1) Interstitial lung disease
2) Vascular disease
“Scleroderma Lung”
1. Interstitial Lung Disease A) nonspecific interstitial pneumonia (NSIP) pattern B) interstitial fibrosis 2. Concentric arterial thickening ~67%get interstitial lung disease ~20% get pulmonary hypertension
IL-8
scleroderma lung, early, neutrophil attractant and activator
TNF
scleroderma lung, early, neutrophil attractant and promoter of neutrophil-endothelial binding
MIF1alpha
scleroderma lung, promoter of neutrophil chemotaxis
RANTES
scleroderma lung, acronym for regulated on activation normal T cell expressed and secreted
-T cell recruiter and activator
Endothelin-1
scleroderma lung, vasoconstrictor
TGF-beta
scleroderma lung, late, promoter of fibroplasia
Location of Scleroderma Lung
-favors bases, posterior & periphery
CT: ground-glass, then reticular infiltrates
Scleroderma Lung Micrograph
- most common pattern of early disease is nonspecific interstitial pneumonia (NSIP) with lymphocytes and microphage infiltrating interstitium -fibroblasts + collagen = interstitial fibrosis
- similar to UIP pattern, tell by temporal homogeneity (all areas at same stage)
Why distinguish NSIP “pattern” from NSIP?
different treatment
What stain to see systemic sclerosis?
Trichrome stain - extensive excess collagen stained blue
“Scleroderma lung” vascular disease
- concentric thickening & fibrosis of small pulmonary arteries
- causes pulmonary hypertension & cor pulmonale
- can occur w/o interstitial lung disease (CREST, anti-centromere)
Systemic Sclerosis: Symptoms
- Dyspnea (55%), increased work of breathing (stiff lungs) - sensed by respiratory muscle mechanoreceptors
- Dry cough (<50%)
Systemic Sclerosis: Signs
-dry inspiratory “velcro” crackles, especially at the bases, initially subtle “fine” thought to represent the sudden opening of small airways abnormally closed by the pressure of interstitial inflammation, edema and fibrosis around them
Systemic Sclerosis: Diagnosis
- association of symptoms, signs and radiology of interstitial lung disease with skin, esophageal and renal manifestations of scleroderma and/or renal manifestations of scleroderma and/or anti-Scl70 (anti-DNA topoisomerase abs (40%)
- restrictive pattern abnormalities due to reduced compliance and decreased diffusing capacity due to alveolar-capillary block or pulmonary hypertension on pulmonary function tests
- Open lung biopsy if needed*
Systemic Sclerosis: Treatment
Cyclophosphamide NOT steroids
-steroids = scleroderma renal crisis
NSIP: Treatment
steroids
Systemic Sclerosis: Prognosis
mean: 12 years
Death rate 3.9%/year men
2.6%/year women
-cause of death, scleroderma lung disease (60%)
Lupus
1) Pleuritis
2) Acute lupus pneumonitis
3) nonspecific interstitial pneumonia
4) pulmonary vascular disease
- concentric arterial thickening
- pulmonary thromboembolism
5) Shrinking lung syndrome
Pleuritis
Lupus
-most common pleuropulmonary manifestation of lupus
20% at onset, 50% over time, 100% autopsy
-often asymptomatic, but sometimes have pleuritic chest pain, which can be recurrent or intractable
Lupus Pleuritis
fibrinous: +/- associated serosanguinous exudative pleural effusions
- few inflammatory cells in exudate
- ANA in pleural fluid
Fibrinous Pleuritis
- partly organized by fibroblasts and densely adherent, but partly peeled off
- pleural effusions of lupus usually small and bilateral
Pleuropulmonary disease of lupus
1) broader spectrum (more types)
2) more commonly acute than any other autoimmune connective tissue disease (collagen vascular disease)
Acute Lupus Pneumonitis
1) rare (2% of lupus patients)
2) actually a form of acute lung injury (diffuse alveolar damage)
3) can take form of diffuse hemorrhage
Acute Lupus Pneumonitis Micrograph/Disease Progression
- alveolitis with loose fibrin exudate & lymphocytes & macrophages in airspaces and a few lymphocytes in interstitial
- can be hemorrhagic
- goes on to interstitial pneumonia & fibrosis
Acute Lupus Pneumonitis: Symptoms
dyspnea, fever, cough
Acute Lupus Pneumonitis: Signs
fever, wet pulmonary crackles
Acute Lupus Pneumonitis: CT
diffuse ground-glass opacification (+ pleural effusion, 50%)
Acute Lupus Pneumonitis: Diagnosis
symptoms, + signs, + CT findings, + context (demographic + serology)
Acute Lupus Pneumonitis: Treatment
steroid + immunosuppression
Acute Lupus Pneumonitis: Prognosis
50% mortality
Nonspecific interstitial pneumonia
~2% at onset
<5% over time
similar to NSIP without lupus
Pulmonary Vascular Disease with Lupus
- 10% of lupus patients have subclinical evidence of pulmonary hypertension on echocardiography
- need to differentiate which of the 2 types a patient has, conc. on arterial thickening or thromboembolic disease
Thromboembolic disease
-associated with “lupus anticoagulant” or anti-phospholipid antibodies
Chronic Pulmonary Thromboembolic Disease
- not specific for lupus
- pulmonary artery webs, strands of fibrous tissue spanning the lumen = old (organized) pulmonary emboli
Shrinking Lung Syndrome with Lupus
Rare, due to diaphragmatic weakness Syndrome: 1) dyspnea 2) small lungs on x-ray 3) decreased diffusing capacity (DLCO) 4) restrictive pattern PFT abnormalities -usually self limited
Pleuropulmonary Disease in RA
-14% have “significant” disease, 44% subclinical
-3X more in males
-more common in smokers
Types:
1) pleuritis +/- pleural effusion
2) fibrosing interstitial lung disease
3) follicular bronchiolitis
4) obliterative bronchiolitis
5) organizing pneumonia
6) acure lung injury
7) pulmonary hemorrhage
8) rheumatoid nodules
Pleuritis with fibrinous pleural effusion
20% RA patients have pleuritic pain
<5% pleural effusions
50% pleural disease at autopsy
RA related disease on microscope
- abundant lymphocytes and germinal centers
- commonly involves the bronchioles
- commonly involves pleura
UIP Pattern fibrosing interstitial lung disease
Temporally Heterogeneous:
1) early levels of only inflammation
2) late areas of only fibrosis
3) intermediate areas with mix of inflammation, repair, fibrosis
- fibrotic lung remodeling that juxtaposes normal lung with honeycomb lung (end-stage)
UIP Pattern fibrosing interstitial lung disease
Location
-most severe in periphery(subpleural) and lower lobes (basal lower lobes)
Follicular bronchiolitis
-more common with RA
CT: peri-bronchial or centrilobular nodes and ground-glass opacities in bronchocentric distribution
-responds to steroids
Obliterative Bronchiolitis
- more common with RA
- obstructive pattern PFTs
- sometimes=superimposed Sjogren’s
- does NOT respond to steroids
Organizing Pneumonia
- more common with RA
- present with acute onset, fever, alveolar infiltrates
Interstitial Pneumonia plus acute lung injury
edema
hyaline membranes
Interstitial Pneumonia plus acute lung injury
Micrograph
- Rheumatoid nodule in lung with large area of necrosis
- higher power showing rim of palisading histiocytes, basophilic debris and surrounding fibrosis, lymphocytes, macrophages and multinucleate giant cell
Methotrexate
used to treat rheumatologic diseases (RA)
Pneumonitis
adverse affect of methotrexate
-due to cytotoxicity causing diffuse alveolar damage or hypersensitivity causing chronic interstitial pneumonia (similar microscopic features)
Methotrexate Pulmonary Toxicity
Early
not to bad, patchy lymphocytic interstitial infiltration
Methotrexate Pulmonary Toxicity
Late
bad, fibrotic
Methotrexate Pulmonary Toxicity
- life-thretening (20% mortality)
- responds to steroids
- subacute (first 4 months)
- dyspnea, cough, fever
- bilateral pulmonary crackles
Methotrexate Pulmonary Toxicity CT
bilateral, ground glass, reticular opacification
worse: coarser, denser, more reticular
Pulmonary Toxicity of RA
1) acute chronic lung injury or chronic interstitial pneumonia
2) Penillamine: alveolar hemorrhage
3) Anti-tumor necrosis factor lpoagents, interstitial pneumonia
Polymyosisit/dermatomyositis associated lung disease - Similarities to other CTD
-chronic
-NSIP
-dyspnea
-ground glass/reticular infiltrates
-restrictive pattern (PFT abnormalities, decreased DLCO)
-present with acute lung injury
Treat: steroids +/- immunosuppression
Polymyosisit/dermatomyositis associated lung disease - Differences
- occurs in 70% of patients
- most common cause of death
- ILD + organizing pneumonia
- consolidation on CT scan (50%)
- resp. failure from muscle weakness
- anti-synthase syndrome: myositis + arthritis + lung disease
- 12% patients have malignancy
Sjogren Syndrome Similarities `
- most common symptom is dyspnea (10%)
- most common CT: ground glass lower lobe
- is nonspecific interstitial pneumonia
Sjogren Syndrome Differences
- in 11% of patients
- involves airways: submucosal glands
- xerotrachea, xerobronchea
- loss of submucosal gland secretion - relentless dry cough
- bronchial hyper responsiveness like COPD
Sjogren’s syndrome-associated NSIP
1) lymphoid follicles (germinal centers)
2) bronchiolocentric
3) more lymphocytes
4) macrophages/multinucleated giant cell
Type of NSIP in Sjogren’s syndrome?
“cellular”
Type of interstitial pneumonia in Sjogren’s syndrom?
“lymphocytic” “lymphoid”
-lots of lymphocytes that replicate and make mistakes - may have lymphoma
Chronic Pheumonia: interstitial
Pneumocysits
Sarcoidosis
Toxoplasmosis
Chronic Pheumonias: nodular
TB histoplasmosis aspergillosis cryptococcosis coccidioidomycosis blastomycosis
Acute lung disease in RA patient is?
Infectious
Subacute or chronic dyspnea in RA patient?
rheumatologic
Nodular lung disease in RA patient?
infectious or neoplastic
