Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
89 Cards in this Set
- Front
- Back
|
Chronic Interstitial Pneumonias
|
1. Non-caseating Granulomatous Lung Diseases
2. Usual Interstitial Pneumonia (UIP) 3. Nonspecific Interstitial Pneumonia (NSIP) 4. Desquamative Interstitial Pneumonia (DIP) |
|
|
Non-caseating Granulomatous Lung Diseases
|
1. Sarcoidosis
2. Hypersensitivity Pneumonitis (HP) |
|
|
Sarcoidosis
Clinical Features |
Multiorgan disease
Most frequently affects: - Lungs (90-95%) - Lymphatic system - Liver, spleen, eyes and other organs Wide variety of signs and symptoms - Asymptomatic (most common presentation) > Incidental finding on a routine CXR - Symptomatic > Dyspnea with or without exertion > Nonproductive cough > Nonspecific chest pain |
|
|
Sarcoidosis
Epidemiology |
Young adults 20-40 (most common)
Slight female predominance >> in African-Americans (US) >> Irish and Scandinavians (outside US) |
|
|
Sarcoidosis
Diagnosis |
Clinical and radiologic findings supported by interstitial NONCASEATING GRANULOMAS IN A LYMPHATIC AND BRONCHOVASCULAR DISTRIBUTION
Exclusion of other disorders which cause granulomatous disease |
|
|
Sarcoidosis
Pathogenesis |
UNKNOWN, but several immunologic features observed:
1. HEIGHTENED/EXAGGERATED HELPER T-CELL TYPE 1 (Th1) IMMUNE RESPONSE TO UNIDENTIFIED ANTIGEN (self or foreign) AT SITES OF DISEASE 2. Depression of cutaneous delayed-type hypersensitivity 3. Elevated circulating immune complexes & signs of B-cell hyperactivity |
|
|
Sarcoidosis
Granulomatous Reaction Characterized |
Helper/inducer T lymphocytes
- Exhibit marked cellular immune response - Accumulate in affected organs - Secrete lymphokines [interferon gamma and interleukin 2 (IL-2)] and recruit macrophages - Participate in formation of noncaseating granulomas Involved tissues (containing sarcoid granulomas) - Helper/inducer to suppressor/cytotoxic T-cell ratio of 10 to 1 Uninvolved tissues - Helper/inducer to suppressor/cytotoxic T-cell ratio of 2 to 1 Sarcoid alveolar macrophages - Behave as secretory cells - Release great variety of cytokines - Tumor necrosis factor-alpha, IL-12, IL-15, and growth factors |
|
|
Sarcoidosis
Hyperglobulinemia Characterized |
Nonspecific polyclonal activation of B cells by helper T cells
Typical of ACTIVE sarcoidosis |
|
|
Sarcoidosis
Laboratory Tests |
No specific lab test
- Serum level of angiotensin converting enzyme (ACE) elevated (2/3 of patients) - 24-hour urine calcium excretion frequently increased (Calcium is elevated) |
|
|
Sarcoidosis
Later Stages in Lungs |
Interstitial fibrosis
Cavitary lesions Honeycomb change Subpleural cysts (especially apex of this upper lobes) |
|
|
Sarcoidosis
Histologic Features Pertinent Negatives |
LACK OF ORGANISMS ON CULTURES OR SPECIAL STAINS
Lack of exposure to mineral dust such as beryllium, talc, or aluminum Paucity of interstitial chronic inflammation |
|
|
Sarcoidosis
Histologic Features Major Features |
NONCASEATING GRANULOMAS
Characteristics: well formed or tightly packed, may become hyalinized Distribution: along lymphatic routes—bronchovascular bundles, pleura, and septa |
|
|
Sarcoidosis
Histologic Features Minor Features |
Vasculitis in up to 2/3 of open lung biopsies
Punctate necrosis in up to 1/3 of open lung biopsies Inclusions - Schaumann bodies - Asteroid bodies - Birefringent calcium carbonate or calcium oxalate crystals - Microcalcifications - Hamazaki-Wesenberg bodies |
|
|
Sarcoidosis
Histologic Features Complications |
Interstitial fibrosis with honeycombing in advanced stages
Cavitation/cystic changes Aspergillomas |
|
|
Sarcoidosis
Bronchiole Submucosa |
Noncaseating granuloma with a nodular cluster of epithelioid cells and giant cells
|
|
|
Sarcoidosis
Noncaseating granulomas |
Infiltrating pleura and the interlobular septa
Surrounded by concentric fibrosis |
|
|
Schaumann body
|
Concentric laminated calcification within a granuloma
Inclusions seen in sarcoidosis |
|
|
Asteroid Body
|
Within Macrophages
Looks like a spider Inclusions seen in sarcoidosis |
|
|
Sarcoidosis
Common Treatment |
Corticosteroids
- Severe symptoms, persistent pulmonary opacities, hypoxemia, and severe lung function impairment - Extrapulmonary manifestations including ocular disease, hypercalcemia, cardiac dysrhythmia, neurologic involvement, arthritis, and disfiguring skin lesions - Aspergilloma is complication which may result in life-threatening pulmonary hemorrhage |
|
|
Mortality secondary to sarcoidosis occurs
|
- 1 to 5 percent of patients
- Usually secondary to lung, central nervous system, or cardiac involvement |
|
|
Sarcoidosis
Alternative Treatments |
Immunosuppressive, cytotoxic, and antimalarial drugs
Specific agents include: - Methotrexate, azathioprine, cyclophosphamide, colchicine, chlorambucil, cyclosporine, chloroquine, hydroxychloroquine, nonsteroidal anti-inflammatory drugs, and pentoxifylline Radiation (neurosarcoidosis) Organ transplantation - Endstage hepatic, renal, cardiac, or respiratory failure complicating sarcoidosis |
|
|
When should you treat sarcoidosis?
|
Deciding when to treat sarcoidosis can be difficult b/c almost 50 percent spontaneously remit
|
|
|
What is the other name for hypersensitivity pneumonitis?
|
Extrinsic Allergic Alveolitis
|
|
|
Hypersensitivity Pneumonitis
|
Diffuse interstitial granulomatous lung disease
Represents IMMUNOLOGIC REACTION TO INHALED ORGANIC ANTIGENS or, rarely simple chemicals Complex syndrome of varying intensity, clinical presentation, and natural history rather than a single, uniform disease |
|
|
Hypersensitivity Pneumonitis
Clinical Features |
Symptoms may develop HOURS, WEEKS OR MONTHS after exposure
History of allergic disease UNCOMMON - Not predisposing factor for development of HP Persons with mild or subclinical HP - Often misdiagnosed as suffering viral illnesses or asthma - Either of which may have nonspecific clinical findings which mimic HP |
|
|
Hypersensitivity Pneumonitis
Prevalence/Incidence |
Unknown
Vary from country to country and within certain regions of a country Vary due to the local climate, season, geographic conditions, local customs, and the presence of industrial manufacturing plants Farmer's lung Bird fancier’s lung Only small fraction exposed to potential antigens that cause HP actually develop clinical disease - Only after the weeks to months of exposure required to induce sensitization |
|
|
Hypersensitivity Pneumonitis
Farmer's lung |
Most common in cold, wet climates
Varies with local farming practices One of the most common forms of HP |
|
|
Hypersensitivity Pneumonitis
Bird fancier’s lung |
Prevalence higher among bird fanciers than among farmers because contact with the inciting avian antigens is less limited by season or geographic location
|
|
|
Hypersensitivity Pneumonitis
Immunologic Factors |
Combination of:
- Immune complex–mediated (type III) and - T cell–mediated, delayed (type IV) hypersensitivity reactions Precipitating IMMUNOGLOBULIN (Ig) G ANTIBODIES against offending agent in serum (most cases) Caveat: Large majority with serum precipitins to inhaled antigens do not develop HP on exposure, suggesting a genetic component in host susceptibility |
|
|
Is Hypersensitivity Pneumonitis Acute, Subacute or Chronic?
|
All three
|
|
|
Acute Hypersensitivity Pneumonitis
|
Not well known
Neutrophilic infiltrate in alveoli and respiratory bronchioles (acute bronchiolitis) Sometimes pattern of DAD Temporally uniform, nonspecific, chronic interstitial pneumonia commonly seen |
|
|
Subacute Hypersensitivity Pneumonitis
|
Lymphocytic interstitial pneumonitis, granulomas, organizing pneumonia, and fibrosis
|
|
|
Chronic Hypersensitivity Pneumonitis
|
Most biopsies performed at this stage
Distinctive histologic appearance |
|
|
Diagnostic Triad of Chronic Hypersensitivity Pneumonitis
|
1. (Most common) TEMPORALLY UNIFORM chronic interstitial inflammation with PERIBRONCHIOLAR ACCENTUATION
- BRONCHIOLOCENTRIC CELLULAR INTERSTITIAL PNEUMONIA 2. (Two thirds) Nonnecrotizing POORLY FORMED granulomas in peribronchiolar interstitium 3. (Two thirds) Foci of BOOP/COP - Intraluminal budding fibrosis or organizing pneumonia |
|
|
Progression of
Hypersensitivity Pneumonitis |
May result in nonspecific fibrosis resembling UIP
Must examination of less fibrotic areas where characteristic lesions of cellular bronchiolitis, granulomas, or intraluminal fibrosis are more likely to be found |
|
|
Pathologic Features of
Hypersensitivity Pneumonitis |
Occasional lymphoid aggregates
- Not prominent Foamy macrophages - Common - Within peribronchiolar airspaces - Prominent in approximately 5% Crystalline inclusions or cholesterol clefts - Seen within giant cells Pleural fibrosis CRYPTOSTROMA CORTICALE - maple bark stripper's disease |
|
|
How is a dx of Hypersensitivity Pneumonitis made?
|
Biopsy findings can only suggest
Ultimate diagnosis of HP - Correlation with clinical - Identification of offending antigen |
|
|
Differential Diagnosis
Hypersensitivity Pneumonitis |
Must be separated histologically from other conditions:
- Infection, sarcoidosis, UIP, and NSIP - Special stains > Rule out acid-fast bacilli, fungi, and Pneumocystis carinii. NSIP - Presence of granulomas and exposure history Collagen vascular disease and drug reactions - Clinical information required to exclude |
|
|
Hypersensitivity Pneumonitis
Treatment |
1. Removal of causative antigen
2. Removal of causative antigen 3. Removal of causative antigen 4. Corticosteroids - Acute, subacute, and chronic HP - Accelerate initial recovery from farmer's lung and bird fancier's lung (severely ill patients) - Long-term outcome for farmer's lung unchanged |
|
|
Hypersensitivity Pneumonitis
Prognosis |
Majority near total recovery of lung function
- May take several years after the inciting exposure ceases Bird fanciers have a worse prognosis than farmers with HP - May be due to higher exposure to the HP antigens and persistence of avian antigens in home environment Irreversible once dense fibrosis develops with honeycomb changes |
|
|
What are other names for Usual Interstitial Pneumonia (UIP)?
|
Chronic interstitial pneumonitis
Cryptogenic fibrosing alveolitis |
|
|
Pathologic pattern of UIP corresponds to the clinical diagnosis of
|
Idiopathic Pulmonary Fibrosis (IPF)
|
|
|
Usual Interstitial Pneumonia
|
Insidious onset of dyspnea with chronic, progressive downhill course (long term may many, many months)
Males >> Females Age between 50 and 70 years of age - Approximately two thirds over age 60 at time of presentation |
|
|
Usual Interstitial Pneumonia
Etiology |
No distinct geographic
No predilection by race or ethnicity Potential genetic role - Supported by the findings of familial cases Cigarette smoking 1.6- to 2.3-fold excess risk Long-term exposure to metal dust or wood dust independent risk factor No cultural, serologic, or morphologic evidence viral etiologies |
|
|
UIP Etiology
|
No distinct geographic
No predilection by race or ethnicity Potential genetic role - Supported by the findings of familial cases Cigarette smoking 1.6- to 2.3-fold excess risk Long-term exposure to metal dust or wood dust independent risk factor No cultural, serologic, or morphologic evidence viral etiologies |
|
|
TGF-β1
UIP |
NEGATIVELY REGULATES TELOMERASE ACTIVITY
Facilitates epithelial cell apoptosis, cycle of death and repair Influences multiple pathways that regulate pulmonary fibrosis |
|
|
UIP
Pathogenesis |
Intrinsic abnormality of tissue repair
Evidence: Familial pulmonary fibrosis have mutations that SHORTEN TELOMERES TGF-β1 Caveolin-1 |
|
|
Caveolin-1
UIP |
Regulated by TGF-β1
Predominant structural protein of caveolae, flask-shaped invaginations of the plasma membrane present in many terminally differentiated cells ENDOGENOUS INHIBITOR OF PULMONARY FIBROSIS Limiting TGF-β1–induced production of extracellular matrix Restoring alveolar epithelial repair processes Decreased in epithelial cells and fibroblasts of IPF patients - Such down-regulation may be mediated by the ability of TGF-β1 to attenuate the expression of caveolin-1 in fibroblasts Overexpression in mouse models limits fibrosis |
|
|
UIP
Targeted Therapy |
Therapeutics directed toward:
1. Neutralizing TGF-β1 2. Enhancing telomerase activity 3. Delaying telomere shortening, 4. Augmenting caveolin-1 |
|
|
UIP
Physical Examination |
Rarely normal
Most tachypneic, with rapid shallow breaths, probably because of increased work of breathing Crackles bibasilar, late inspiratory, fine crackles ("velcro" rales) Clubbing, pulmonary hypertension and cyanosis are late manifestations, indicative of advanced disease |
|
|
UIP Tests
|
Pulmonary function tests
- Restriction and impairment of gas exchange - Lung volumes (TLC, FRC, and RV) reduced - Lung compliance decreases (b/c of fibrosis) - DLCO is reduced Arterial blood gases - Resting > Hypoxemia > Respiratory alkalosis (b/c of shallow breaths) - Exercise > Widening of the alveolar-arterial PO2 difference ([A-a]PO2) with arterial PO2 and oxygen saturation (SO2) falling |
|
|
UIP
Targeted Therapy |
Therapeutics directed toward:
1. Neutralizing TGF-β1 2. Enhancing telomerase activity 3. Delaying telomere shortening, 4. Augmenting caveolin-1 |
|
|
UIP
Physical Examination |
Rarely normal
Most tachypneic, with rapid shallow breaths, probably because of increased work of breathing Crackles bibasilar, late inspiratory, fine crackles ("velcro" rales) Clubbing, pulmonary hypertension and cyanosis are late manifestations, indicative of advanced disease |
|
|
UIP Histology
Major Features |
PATCHY lung involvement
TEMPORALLY HERTEROGENEOUS (scattered interstitial fibroblastic foci adjacent to more advanced collagen) Interstitial process MOST PROMINENT IN SUBPLEURAL AND PERIPHERAL LOBULAR REGIONS (not usually bronchocentric) Dense fibrosis with remodeling of lung architecture with frequent “honeycomb” fibrosis Mild/moderate interstitial inflammation |
|
|
UIP Histology
Negative Features |
Absence of other interstitial lung diseases (i.e., UIP is a diagnosis of exclusion)
Granulomas absent or inconspicuous Lack of marked interstitial inflammation |
|
|
UIP
Early Pathologic Features |
1. firm lungs
2. pulmonary edema 3. hyaline membranes 4. mononuclear infiltration 5. type II pneumocyte hyperplasia - looks just like DAD |
|
|
UIP
Later Pathologic Features |
1. fibrous tissue
2. fibrogenic foci (areas of active disease) 3. thickened alveolar septa (solid and normal lung) 4. hyperplastic smooth muscle microcysts 5. loss of alveolar capillaries |
|
|
UIP
End Stage Pathologic Features |
1. spaces lined by cuboidal/columnar epithelium separated by fibrosis and forming honeycomb lung (particularly in the superior portion of lobes)
2. also lymphoid hyperplasia 3. thickening of intima and media of pulmonary arteries |
|
|
UIP
Diagnosis |
Requires open lung biopsy!
Transbronchial biopsy inadequate! - Malignancy, infections, sarcoidosis, hypersensitivity pneumonitis, cryptogenic organizing pneumonia, eosinophilic pneumonia, or Langerhans' cell histiocytosis Correlate to radiology! - 50% have UIP pattern on HRCT Correlate to clinical and exclude other entities! |
|
|
UIP and Lung Carcinoma
|
13 to 31% of patients
Prominent reactive epithelial proliferations versus well-differentiated adenocarcinomas - Separation sometimes difficult Features favoring adenocarcoma - Exuberant micropapillary proliferation of glandular epithelium - Relatively sparse inflammation - Prominent mucinous epithelium - Invasive growth - Cytologic atypia |
|
|
UIP
Differential Diagnosis |
Fibrotic phase of HP
- Potentially confused with UIP - Pattern of temporal heterogeneity with dense fibrosis and scattered fibroblastic foci may be seen in HP - Presence of granulomas and/or intraluminal fibrosis (clues) |
|
|
Worse prognostic factors of UIP
|
Eosinophilia
Increased fibroblastic foci |
|
|
UIP Prognosis
|
Median survival from diagnosis is 3 years
|
|
|
Treatment of UIP
|
20% improve with Steroids
|
|
|
Nonspecific Interstitial Pneumonia
Incidence/Prevalence |
Less frequent than UIP
Much more common than other idiopathic interstitial pneumonias More common in women than in men Correlated with smoking history |
|
|
Nonspecific Interstitial Pneumonia
Average duration of illness prior to diagnosis |
8 to 18 months
|
|
|
Nonspecific Interstitial Pneumonia
Average age |
Ranges from 46 to 57
has been found in children |
|
|
Nonspecific Interstitial Pneumonia
Pattern found in younger patients |
Idiopathic NSIP, cellular pattern
Younger (mean 39, range 26–50) than idiopathic UIP |
|
|
Nonspecific Interstitial Pneumonia
Pattern found in older patietns |
Idiopathic NSIP, fibrosing pattern
(mean 50, range 30 to 71) |
|
|
NSIP
Etiologic Considerations |
Cause Unknown
Collagen vascular/connective tissue disease - Strong association with NSIP - Especially SLE, polymyositis, dermatomyositis, scleroderma, Sjogren’s syndrome, and rheumatoid arthritis. Drug reaction - Especially nitrofurantoin, amiodarone Idiopathic |
|
|
NSIP
Most common symptoms |
- Exertional dyspnea
- Cough - Fever similar to other idiopathic interstitial pneumonias (esp. UIP) |
|
|
NSIP
Physical Exam |
Crackles on chest auscultation
Clubbing |
|
|
NSIP
Routine Laboratory Studies |
Nonspecific
Antinuclear antigen (ANA) and/or rheumatoid factor positive (minority) |
|
|
NSIP
Radiologic Features |
Variable and nonspecific
(Most common) Areas of consolidation or hazy increased opacity (ground-glass opacities) - May be diffuse - Tend to involve mainly the lower lobes Mimics DIP and hypersensitivity pneumonitis; occasionally BOOP or UIP |
|
|
NSIP
Pathologic Features |
TEMPORALLY UNIFORM interstitial inflammatory and fibrosing process
Containing varying proportions of inflammation and fibrosis USUALLY DIFFUSE INVOLVEMENT OF THE LUNG - Sometimes process patchy |
|
|
NSIP
Cellular Pattern |
Mild to moderate interstitial chronic inflammation causing thickening of alveolar walls. Some alveolar walls spared.
Unlike UIP, ARCHITECTURE IS PRESERVED AND THERE IS NO INCREASE IN DENSE FIBROSIS |
|
|
NSIP
Fibrosing Pattern |
Alveolar walls uniformly thickened by fibrosis.
CONTRAST TO UIP, architecture relatively preserved and fibrosis is about same age, without fibroblast foci |
|
|
Major Histologic Features of NSIP, Fibrosing Pattern
|
Dense or loose interstitial fibrosis lacking the temporal heterogeneity and/or patchy features of UIP
Lung architecture often preserved Interstitial chronic inflammation: mild or moderate |
|
|
Pertinent Negative Histologic Features of NSIP, Fibrosing Pattern
|
Fibroblastic foci: inconspicuous or absent—especially important in cases with patchy involvement and subpleural or peripheral lobular distribution
Lack of airway centricity Granulomas and Eosinophils: inconspicuous or absent Lack of viral inclusions and organisms |
|
|
NSIP
Treatment and Prognosis |
Spontaneous remissions do not occur
- Expected disease progression and shortened survival times (if untreated) Very corticosteroid-responsive - Unlike UIP (for which NSIP most often confused symptomatically), better responsiveness to treatment and prognosis - Improvement or recovery up to 75% (with or without immunosuppressive agents) - Especially if started early phases |
|
|
NSIP
Differential Diagnosis |
Interobserver variability in diagnosis
Considerable overlap with Hypersensitivity Pneumonitis - HP shows presence of granulomas and an exposure history - Some have both HP and NSIP Diagnosis of exclusion - Histologic pattern lacks features of DAD/AIP, idiopathic BOOP/COP, UIP, or DIP |
|
|
Desquamative Interstitial Pneumonia
Clinical Features |
Approximately 90% of patients are cigarette smokers
Clinical presentation similar to UIP - Subacute (weeks to months) - Insidious onset of dyspnea and cough |
|
|
Desquamative Interstitial Pneumonia
Etiology |
More commonly male; male to female ratio of 2 to 1
Middle aged adults most often affected - Fourth to fifth decade of life Rare cases in children - Probably different disorder than adult DIP - Surfactant deficiency or alveolar proteinosis which show prominent alveolar macrophage accumulation |
|
|
Desquamative Interstitial Pneumonia
Physical examination |
Shows crackles on auscultation of chest not as prominent as other idiopathic interstitial pneumonias
Clubbing |
|
|
Desquamative Interstitial Pneumonia
Tests |
Laboratory investigations
- Usually unremarkable Lung function tests - Restrictive pattern with reduced DLCO - Hypoxemia on arterial blood gas analysis Broncheo Alveolar Lavage - Marked increase in total cells recovered - Predominance of macrophages. |
|
|
Desquamative Interstitial Pneumonia
Therapy |
Cessation of smoking
- Often leading to spontaneous regression - Recurrence if patient starts smoking or is exposed to passive smoke Corticosteroid therapy - Moderate to severe symptoms and gas exchange abnormalities - Better response than UIP Lung transplantation in endstage disease from DIP - Disease recurrence in transplanted lung has been reported |
|
|
Desquamative Interstitial Pneumonia
Prognosis |
Much better than other idiopathic interstitial pneumonias, especially UIP
Progression (small subset) Fulminant DIP leading to death rare |
|
|
What is the DIP Caveat (where should you look)?
|
Focal DIP-like reactions can be seen around mass lesions, such as INFARCTS or TUMORS
|
|
|
Histologic hallmarks of
Desquamative Interstitial Pneumonia (DIP) |
Diffuse, marked, INTRA-ALVEOLAR MACROPHAGE ACCUMULATION
- Accentuated around respiratory bronchioles - May extend diffusely throughout the lung parenchyma Minimal fibrosis with only mild or moderate thickening of the alveolar walls NO SCARRING FIBROSIS CAUSING REMODELING OF THE LUNG ARCHITECTURE (unlike UIP) Fibrous connective tissue same age Fibroblastic foci are absent or inconspicuous |
