L30 Diffuse Parenchymal lung disease (part II)

• Rheumatoid Arthritis
• Systemic Lupus Erythematosis
• Systemic scleraderma
• Polymyositis-dermatomyositis (Anti-synthetase syndrome)
• Sjögren's syndrome
• Wegner's granulomatosis
• Goodpasture's sysndrome

• Can present with:
• -Effusions
• -Nodules
• -Rounded atelectasis
• -Bronchiolitis
• -Bronchiectasis
• - Interstitial fibrosis (although, usually mild)

Pts often on Methotrexate for RA, some data shows MTX can cause interstitial fibrosis

• -Acute pneumonitis
• -Interstitial fibrosis
• -Serositis (fluid in the pleural space or pericardium)
• --> pleurisy or pericarditis
• -Chest pain
• "shrinking lung syndrome" = progressive decrease in lung volume; CT shows lung pulling away from pleura (swirling star appearance)

• Severe fibrosis
• Pulmonary arterial hypertension

• interstitial fibrosis
• Bronhiolitis obliterans with organizing pneumonia (BOOP)
• Respiratory muscle weakness--> respiratory distress/failure
• Repeated aspiration events from dysphagia

• Interstitial fibrosis
• Lymphocytic infiltration of alveoli
• -lymphocytic interstitial pneumonia (LIP)
• -Lymphoma

• *We"C"ner's granulomatosis
• -c-ANCA
• -C pattern: upper respiratory, lungs, kidneys
• --Also can cause ocular sclerosis, cutaneous vasculitis, neuropathy, arthritis...
• -Anti-"C"rine protease (PR3) - anti-serine protease

• -Small vessel vasculitis, necrotizing granulomatous disease...
• Renal: focal glomerulonephritis
• Pulmonary disease:
• -Necrotizing nasal granlumas (saddle nose deformity, perforated septum)
• 
• -Subglottic stenosis
• -Nodules, infiltrates, cavities:
• 

• c-ANCA
• -Antibody levels correlate with disease activity
• 
• -c: cytoplasmic

• Course:
• -high morbidity/mortality: 90% mortality at 2 years if not treated
• -respiratory failure, pumonary hemorrhage, infections, renal failure, DVT, PE, hearing loss

• Tx: Immunosuppression is mainstay of therapy
• -Steroids, cyclophosphamide, methotrexate, azathioprine, etanercept
• -TMP/SMZ (anti-Staph med)

Rare.

• -Pulmonary hemorrhage (leading to respiratory failure and post-inflammatory fibrosis)
• -Glomerulonephritis:
• -Anti-type IV collagen antibodies

• Presentation:
• -hematuria
• -hemoptysis
• -classically in young, adult males
• Tx: immunosuppression, plasmapheresis

• Sarcoidosis
• Idiopathic pulmonary fibrosis (IPF)
• Nonspecific interstitial pneumonitis (NSIP)
• Cryptogenic organizing pneumonia (COP)
• Desquamative interstitial pneumonitis (DIP)
• Acute interstitial pneumonia (AIP)
• Respiratory bronchiolitis interstitial lung disease (RBILD)

• -Idiopathic granulomatous inflammation
• -Organs: lungs, lymph nodes, eyes, skin, heart, joints, bone, kidneys, brain, liver...

• Demographics:
• -onset: 20-40 year olds
• -♀>♂
• -African Americans, Northern European whites
• -Sarcoid mimic in women who are post breast CA chemotherapy

Etiology: unknown; conflicting data

• Histopathology:
• -Noncaseating granulmoas
• -Absence of organisms, foreign bodies
• -Dx of exclusion
• 
• 

• Staging: based on CXR (or CT sometimes)
• -Stage 0: normal CxR
• -Stage I: lymphadenopathy ONLY
• -Stage II: lymphadenopathy AND parenchymal disease
• -Stage III: Parenchymal disease ONLY (...idea being that LN has burned out)
• -Stage IV: extensive destruction and architectural distortion

• Features:
• -Accelerated 1,25 vit D formation leads to increased absorption (often see calciuria, rarely see hypercalcemia)
• -Angiotensin Converting Enzyme (ACE): can be elevated (useless test)
• -CD4+ predominance in airways and granulmoas (measure CD4+:CD8+ ratio from BAL) --nonspecific
• ----High CD8:CD4 is suggestive of hypersensitivity pneumonitis
• -Löfgren's syndrome: hylar lymphadenopathy, erythema nodosum, fever, arthralgias

• Clinical:
• -Variable presentation
• -PFTs may show restriction and/or obstruction
• -often spontaneous remission (lower stages don't often require treatment; best prognosis for remission)
• -Can progress with significant morbidity/mortality (hard to predict)

• Tx:
• -Corticosteroids are mainstay
• -Steroid-sparing agents (to minimize side effects of steroids): Methotrexate, Azathioprine, Mycophenolate mofetil
• -New therapyies being explored (Inflizimab, etanercept, ustekinumab, golimumab)

Stage II sarcoidosis: lymphadenopathy and parenchymal disease

Stage IV sarcoidosis: extensive destruction and architectural distortion

-Corina and diaphragm are higher than usual due to fibrosis/volume loss

Dx: clinical +/- pathology

• Presentation:
• -Dry cough, insideous exertional dyspnea
• -Dry "velcro" crackles on exam
• ->50yrs old
• -slight male>female
• -military history (?)
• -more common in smokers or former smokers

• Imaging:
• -reticulonodular pattern
• -subpleural honeycombing
• -traction bronchiectasis (due to fibrosis, different from CF bronchiectasis)
• -basilar predominance
• -"ground glass" (sometimes)
• 

• Pathology:
• -Usual interstitial pneumonia (UIP) pattern: =interstitial fibrosis
• =fibroblastic foci
• =paucity of active alveolitis or bronchiolitis
• =absence of granulomas

• Clinical course:
• -Variable
• -may be complicated by PAH, cor pulmonale, clubbing, exertional hypoxemia, syncope, exacerbations
• -Progressive tend to be fatal quickly
• -stable tends to be stable

• Tx: no proven therapy
• -often employ steroids (but seem to make pts worse more often then not)
• -Pirfenidone -fibroblast inhibitor: (not available in US); shows mild survival benefit

• Presentation:
• -younger age, more acute onset than IPF
• -Imaging shows more areas of "ground glass"
• 
• -Areas of active alveolitis on pathology (less fibrosis typically seen)

• Tx: much better response to immunosuppression
• -may stabilize or resolve completely

• -Clinical syndrome (not to be confused with BOOP, which is a pathologic description)
• 
• -NOT associated with other diseases

• Presentation:
• -Acute to subacute
• -may mimic CAP
• -Does not improve with antibiotics
• -Alveolar infiltrates, airway plugging with fibrosis material, bronchiolar inflammation

• Histopathology: airway plugging with fibrinous material
• 

• Tx: steroid therapy (good response):
• Pre:
• 
• Post:
• 

• chronic eosinophilic pneumonia
• pulmonary alveolar proteinosis
• lymphagioleiomyomatosis

≠Acute eosinophilic pneumonia (rapid, febril, sick)

• Presentation:
• -subacute to chronic
• -weight loss, cough, dyspnea, fevers

• CXR: "photo negative" of pulmonary edema
• edema:
• 
• CEP: clear hilum, peripheral opacities
• 

-May see eosinophils on CBC, always seen on BAL

• Tx: very responsive to steroids
• -disease often recurrs after tx tapered off

• -Primary alveolar disease (not of the interstitium)
• -Excessive accumulation of surfactant-derived proteinaceous phospholipids

• Primary: Associated with anti-GM-CSF antibody
• Secondary: varies, often associated with blood malignancy

• CxR: "Crazy paving" pattern on CT
• -not sensitive nor specific
• (not a CT)
• 
• (CT:)
• 

• histology: proteinaceous material in alveoli
• 

• Tx: whole lung lavage
• -Liters of fluid, under general anesthesia
• -performed unilaterally in most cases

-Exogenous GM-CSF (relatively effective in primary PAP)

proliferation of smooth muscle cells, typically involving lymphatics, vasculature, and airways

• Presentation:
• -spontaneous pneumonthorax (cysts rupture)
• -chylous pleural effusion
• -hemoptysis
• -Obstructive or restrictive pattern on PFTs

• Imaging: shows cystic, reticular markings, prominent interlobular lymphatics
• 

• Epidemiology:
• -found almost exclusively in women of childbearing age
• -Estrogen drives smooth muscle proliferation

• Tx: variable effectiveness
• -Anti-estrogen therapy
• -Oophorectomy
• -Tamoxifen

-Lung transplant often required