ILD Flashcards
What is Dermatomyositis associated with?
anti MDA-5 (associated with progressive ILD)
Mi1-2
hyperkeratosis and periungal erythema, dilated nail capillaries
Dermatomyositis is characterized by specific skin manifestations and muscle involvement.
Which antibodies are associated with Antisynthetase syndrome?
anti-jo-1, anti-PL7, anti-EJ
Antisynthetase syndrome is characterized by myositis and proximal muscle weakness.
What markers are used to identify Langerhans cell histiocytosis?
Cd1a, S-100, stellate
These markers are important in the diagnosis of Langerhans cell histiocytosis.
What is a key marker for LAM (Lymphangioleiomyomatosis)?
serum VEGF-D, mTOR mutation; HMB-45 stain positive
These findings are critical for the diagnosis of LAM.
What characterizes Birt-Hogg-Dube syndrome?
cystic; autosomal dominant, cutaneous fibrofolliculomas, renal adenocarcinoma, stain positive follicular (FLCN)
Birt-Hogg-Dube is a genetic disorder associated with skin lesions and increased cancer risk.
What is Pulmonary Benign Metastasizing Leiomyoma (PBML)?
women with history of uterine leiomyoma, spindle cell smooth muscle, can be military, multiple nodules, low or no FDG avidity
PBML is characterized by specific histological features and immunohistochemical positivity.
Fill in the blank: Follicular bronchiolitis is associated with _______.
sjogren, lymphoid hyperplasia of bronchial-associated tissue along bronchi vascular bundles
Follicular bronchiolitis can be related to autoimmune conditions.
What are the histological features of Nodular Lymphoid Hyperplasia?
interfollicular plasma cell, lymphoid, histiocytes on path, mass like, subpleural, cysts
Nodular lymphoid hyperplasia can present as a mass-like lesion in the lungs.
When does Bleomycin toxicity typically occur?
1-6 months after exposure
Risk factors include renal failure, high oxygen levels, and G-CSF administration.
True or False: RA associated lung involvement commonly presents with pleural effusions.
True
RA lung involvement can manifest in various forms including nodules and bronchiectasis.
What is the most common form of ILD associated with rheumatoid arthritis?
UIP (Usual Interstitial Pneumonia)
NSIP (Nonspecific Interstitial Pneumonia) can also be seen but is less common.
What is the prognosis of UIP related to autoimmune disease?
slower to progress and has better prognosis
Compared to other forms of UIP, autoimmune-related UIP tends to have a more favorable outcome.
What is the best treatment for myositis in the context of lung involvement?
Mycophenolate is best, but bad for RA joints
Treatment options need to be tailored based on the patient’s specific conditions.
What is the characteristic triad of idiopathic pulmonary hemosiderosis?
microcytic anemia, recurring hemoptysis, bilateral alveolar opacities without a clear cause (and bland biopsy without vasculitis)
This condition primarily affects children.
What histological finding is associated with Amiodarone-induced pneumonitis?
lipid-laden foamy macrophages in alveolar spaces
This finding is specific to the lung injury caused by Amiodarone.
What condition is characterized by the presence of parotid enlargement, facial nerve palsy, and anterior uveitis?
Heerfordt’s syndrome
Heerfordt’s syndrome is associated with sarcoidosis.
Fill in the blank: Lofgren’s syndrome includes _______.
EN, bilateral lymphadenopathy, migratory polyarthralgias
Lofgren’s syndrome is a form of acute sarcoidosis that often improves with NSAIDs.
What is the association of Interferon gamma receptor deficiency in young patients?
sarcoidosis and NTM
This deficiency can lead to increased susceptibility to certain infections and autoimmune conditions.
What can the end-stage HP resemble?
UIP
End-stage hypersensitivity pneumonitis can have similar radiological and pathological features to UIP.
What genetic predispositions are linked to IPF?
hermansky pudlak, short telomere, autoimmune, surfactant issues, dyskeratosis
VEXAS
autoinflammatory disorder in pediatrics leading to ILD later in life
Vacuoles
E1 ubiquitin activating enzyme
on the X chromosome
with Autoinflammation
Somatic (not passed down)
Erdheim-Chester disease
histiocytosis syndrome
BRAF V600E mutation
Pro-inflammatory cytokines
Sclerotic lesions of long bones
Skin findings
Retroperitonium involvement (like IgG4 disease)
PET-avid
foamy histiocytes
CD1a negative
MNG histiocytes (touton cells) - giant cells
Ddx of Lymphocytic BAL (>25%)
- Sarcoidosis
- NSIP
- HP
- Drug-induced
- CTD
- Radiation
- COP
- Lymphoproliferative disorders
Ddx for Eosinophilic BAL (>25%)
- Eosinophilic pneumonias
- Drug-induced
- BM transplant
- Asthma
- ABPA
- Infectious
- Hodgkin
Exogenous lipoid pneumonia TBBx and BAL findings
lipid-laden macrophages
PAP stain
PAS stain
CD1a stain
PLHC (>5%)
Recommended number of pieces to biopsy when doing surgical lung bx in ILD
2-3 multi-lobe
From areas of active disease
Factors increasing risk of in-hospital mortality in surgical lung bx in ILD
non-elective (16%)
Male sex
increased age
higher comorbidity scores
open vs. VATS
provisional diagnosis of IPF or CTD-ILD
Smoking-related interstitial disease
Respiratory bronchiolitis-interstitial lung disease (RB-ILD)
Desquemative Interstitial pneumonia (DIP)
PLCH langerhan’s
AEP Acute eosinophilic pneumonia
CPFE (combined pulmonary fibrosis and emphysema)
Idiopathic pleuroparenchymal fibroelastosis (iPPFE)
2/2 systemic disease
Upper lobe predominant fibrosis
Can look like UIP but upper lobe, think iPPFE or burnt out HP
Histology and HRCT of UIP
Path: Peripheral patchy fibrosis, FF, honeycombing, +/- inflammation
CT: Subpleural and basal, reticular, traction bronchiectasis, honeycombing. If costophrenic angles are spared, it is not IPF
Histology and HRCT of NSIP
Path: Homogenous, chronic interstitial inflammation/fibrosis
CT: homogenous, GGOs/reticular, subpleural sparing
Histology and HRCT of OP
PAth Patchy, polypoid granulation tissue plugs
CT: patchy consolidations, GGOs, migrating
Histology and HRCT of RB-ILD/DIP
Path: pigmented brownish (smoker’s) macrophages, bronchiolocentric
DIP more busy
CT: vague NODULES patchy to diffuse GGOs
Histology and HRCT of DAD
Hyaline membranes, granulation tissue, organizing/fibroproliferative
CT: diffuse consolidation/GGOs
Histology and HRCT of LIP
Path: lymphoid, plasma cells (very blue)
CT: patchy GGOs, nodules, cystys
Histology and HRCT of PPFE
Path Pleural/subpleural fibroelastosis, septal elastosis
CT: UPPER/subpl fibrosis +/- PTX pneumomediastinum
“Typical” UIP pattern HRCT (4)
- Honeycombing
- Reticular + peripheral traction bronchiectasis/bronchiolectasis
- Basal and subpleural
- Absence of features insonsistent with UIP pattern (extensive consolidations, GGOs, mosaic attenuation, nodules, cysts)
“Definite” UIP histopathologic pattern
- Dense fibrosis/architectural distortion +/- honeycombing
- PAtchy involvement
- Fibroblast foci
- Subpleural +/- paraseptal predominance
- No features suggesting alternative diagnosis (e.g. granulomas)
Difference between “probable” and “typical” UIP
“Probable”: no honeycombing in “probable”
“Intermediate”: diffuse, not basilar or subpleural
Definitive diagnosis of ILD in undetermined type
cryobiopsy
“Acute exacerbation” of IPF
new widespread alveolar abnormality
often precedes death
antifibrotic therpy may help prevent AE in IPF, steroids not likely helpful
Benefit of antifibrotic therapy
Reduces rate of FVC decline (evidence based)
May help with:
- QOL
- Reduce rate of hospitalization
ASCEND Study - Pirfenidone 2014
INPULSIS-1 & 2 - Nintedanib 2014
What did they find?
Decrease rate of FVC decline in both studies
True or false, risk of lung ca is increased in IPF
true
In Non-IPF ILD (Progressive fibrosing ILD and SSc-ILD), what is the role of antifibrotics
Nintedanib can decrease rate of FVC decline (INBUILD trial NEJM 2019 & SENSIS trial NEJM 2019)
Pirfenidone also (maher Lancet 2019) - not as good at decreasing rate of decline of FVC
Classification of “progressive pulmonary fibrosis”
Non-IPF
Decline in DLCO >10%
Decline in FVC >5%
Radiologic progression
Indications for Nintedanib and Pirfenidone
Nintedanib: IPF, SSc-ILD, Chronic fibrosing ILD with progressive phenotype
Pirfenidone: IPF only
“Familial pulmonary fibrosis”
- 2 or more relatives who share common ancestry
- 10-20% of interstitial pneumonia/pulmonary fibrosis
- 25% of familial cases have identifiable gene variant
- Should do genetic testing in those with early onset (<50 yo)
Typical HRCT features of PLCH
upper lobe
bizarre cystic changes
Stains typically seen with PLCH
CD1a, S100, Langerin (CD207)
Management of PLCH
Stop smoking
BRAF inhibitors (vemurafenib) if BRAF-V600E mutation
Cladribine, cytarabine,cobimetinib, MTX
CPFE HRCT and PFT findings
HRCT: upper lobe lung emphysema with lower lobe fibrosis
PFT: Preserved spirometry and lung volumes with low DLCO
High risk for PH and lung ca
RA associated ILD
** UIP is most common **
then NSIP
OP
Can also affect airway (constrictive bronchiolitis), vascular, pleural, associated with pulmonary amyloidosis
Sjogren-ILD
NSIP > LIP > UIP > OP, and amyloid
MALToma
HRCT: cysts and nodules
Antisynthetase-ILD antibodies
Anti-jo 1
Aminoacyl-tRNA synthetase
RA-ILD is highly associated with this high risk behavior
smoking
Antibody associated with SSc-ILD
anti-SCl70, anti-centromere
Treatment for SSc-ILD
1st line MMF
2nd Tocilizumab
3rd line RTX
4th Cyclophosphamide & Nintedanib
5th HSCT
RA-ILD treatment
1st Steroids
2nd MMF, AZA
3rd RTX
4th Abatacept
5th Nintedanib
Sjogren-ILD tx
1st steroids
2nd MMF, AZA
3rd RTX
PM/DM-ILD tx
1st steroids
2nd MMF, AZA, MTX
3rd Tacrolimus, cyclosporine
4th RTX, IVIG
5th Cyclophosphamide
Tx of SLE-ILD
1st steroids
2nd AZA
3rd MMF
4th RTX
5th cyclophosphamide
Significance of IPAF
can’t identify a CTD but they have some positive autoimmune serology
2/3 of clinical or serologic findings
Sarcoid tx if asymptomatic
No treatment, repeat imaging
3 Syndromes of definite sarcoid that do not need biopsy
- Lofgren: E nodosum, bilateral LN, migratory polyarthralgias
- Heerfordt’s: parotid swelling, uveitis, Bell’s palsy)
- Lupus pernio
Diagnostic options for sarcoidosis
Biopsy of most accessible tissue
lymphocytic >15%
CD4/CD8 >4 (highly specific)
EBUS: 80% yield
TBBx 50-90%
Endobronchial bx: 25% yield
Tx of sarcoidosis
prednisone 20-40 mg
2nd line methotrexate
Limit of thickness of cyst wall (to compare to cavities and emphysematous areas)
<2 mm
5 cystic lung diseases
LAM
BHD
PLCH
LIP
Amyloidosis
HMB-45 staining cells correlates with that disease
LAM
Threshold of serum VEGF-D to dx LAM
> 800 pg/mL
PFT in LAM
obstructive, low DLCO
Diagnosis of LAM needs these
- CT
- LAM on biopsy
- renal AML
- chylothorac
- TSC OR elevated serum VEGF >800
treatment of LAM
sirolimus
lung transplant
Birt-Hogg-Dube mutation
FLCN gene
Distribution of cysts in BHD
lower to mid lung fields
If thinking LIP, what serology should you send
workup for Sjogren
HIV
dysproteinemia (polyclonal)
Cysts and nodules, think ___
LIP
Amyloidosis
Follicular bronchiolitis (less cysts) - favorable prognosis
Light Chain deposition disease vs. amyloid
Non-amyloid deposits, does not stain congo red
no zonal predilection
Follicular bronchiolitis
Hyperplastic lymphoid follicles with reactive germinal centers along bronchovascular bundles
Associated with CVID, COPA (cell trafficking issue), and sjogren’s
Tx of light chain deposition disease
chemotherapy
HSCT
Most frequent types of Amyloidosis
AL (primary) - light chain
AA (secondary) - chronic inflammatory disorders - infrequent
Infrequent with ATTR (familial)
Manifestations of Amyloidosis in the lungs
- Diffuse thickening tracheobronchial tree (posterior membrane NOT spared), foci of calcification
- pulmonary parenchyma - nodules (amyloidomas), reticular pattern, predominantly cystic, can be calcified
localized/diffuse pattern - pleural effusion
- intrathoracic adenopathy
- OSA from microglossia
Management of pulmonary amyloidosis
tracheobronchial: bronchoscopic laser and external beam therapy
Nodules: observe
Diffuse parenchymal: treat underlying plasma cell dyscrasia
IgG4 disease diagnosis
Histopathological: (2 of 3 major feature)
1. Dense lymphoplasmacytic infiltrate
2. Fibrosis, at least focally storiform (cart-wheel like)
3. Obliterative phlebitis
Immunohistochemical: Increased IgG plasma cells AND IgG4 to IgG cell ratio
AND
Clinical context (serum IgG4 level 70-80%); response to steroids
Treatment of IgG4 disease
steroids 30-60 mg/d then taper
Rituximab
IBD-related bronchiolitis tx
corticosteroids (inhaled or systemic)
JAK2 inhibitor (prob not on the boards)
PAP etiology (primary)
autoimmune (90%)
GM-CSF production disruption or receptor (anti-GSM-CSF antiboties) –> decreased surfactant
Causes of secondary PAP
acquired macrophage dysfunction (silicoproteinosis, fentanyl patch smoking, hematologic dyscrasias, infections)
Tx of PAP
whole lung lavage (benefit 15 mo)
GM-CSF SQ daily, nebulized BID q other week
Rituximab
?Statin
PAP can recur after lung transplant
WHat is pulmonary alveolar microlithiasis
intraalveolar deposition of concentrically lammellated calcium phosphate spheres
Dx teen-50yr
CT: calcific micronodular infiltrate on imaging; “sandstorm” with black pleural line
AR genetic: mutation SLC34A2 for typeIIb sodium phosphate cotransporter
Tx lung transplant
Long bones pain, ILD, think ___
Erdheim-Chester Disease
Diffuse Pulmonary Lymphangiomatosis
present with chyloptysis, cough, wheezing
HRCT: septal thickening that is smooth, GGOs, mediastinal infiltration
Dx SLBx
Management sirolimus? bevacizumab? propranolol?
Timing of radiation pneumonitis
4-12 weeks after radiation
Timing of radiation FIBROSIS
6-12 mo after irradiation (straight line effect)
Timing of radiation OP
1-12 mo (usually within 6 mo)
OUTSIDE of the radiation field
Responds well to glucocorticoids
Seen in women with breast ca
Constrictive bronchiolitis (BOS)
allograft recipients
Severe obstructive lung diasease
inhalational injury - fumes, vaping
DIPNECH
Swyer James McLeod (idiopathic constrictive bronchiolitis after infection, UNILATERAL)
What is DIPNECH (what, imaging, dx, tx)
Diffuse infiltrative pulmonary neuroendocrine cell hyperplasia
Associated with constrictive bronchiolitis
mosaic pattern HRCT - tiny nodules
Dx lung biopsy
Tx: somatostatin?
Constrictive bronchiolitis
obstructive
if very severe, insp/exp CT will not be too different due to extent of hyperinflation
Management of constrictive bronchiolitis
Macrolides, inhaled ICS-formoterol?
Transplant
recurrent infection, lower lobe L>R consolidations, think ___
Bronchopulmonary sequestration
usually 1st year of life, recurrent pulm infections, multiple cysts, connected to tracheobronchial tree, pulmonary arterial supply. Dx?
Congenital pulmonary airway malformation (CPAM)
What is TGF-beta associated with
fibroblasts and IPF
WHat is IL-13 associated with
T-cells, IgE, asthma
What is IL-2 associated with
T cells, B cells, melanoma, renal cell Ca
Which stage of ABPA is when pt achieves remission
Stage II (sx resolution, reduced IgE)
Other stages:
1 - acute (elevated IgE, asthma, eosinophilia, opacities, precipitating Ab)
3- Exacerbation (increased IgE and sx recurrence)
4- steroid dependent asthma, elevated IgE
5- fibrotic lung disease
Tx of ABPA
corticosteroids
Itraconazole for ~16 weeks; or vori
Limited evidence for omalizumab
Loeffler Syndrome
simple pulmonary eosinophilia from PARASITES
(Ascaris, hookworms, strongyloides)
Migratory opacities
Pathology: eos infiltrates
usually self-limited, may need corticosteroids but CAUTION if you think it’s strongy
Timing of drug-induced AEP
febrile illness <5d
BAL >25% eos or eosinophilic pneumonitis on bx
Idiopathic acute eosinophilic pneumonia is associated with ___
recent onset of smoking
Dust
Environmental stimuli
WTC
vaping
Chronic eosinophilic pneumonia is associated with ___
asthma
Microabscesses and non-caseating granuloma on path
% of eos on BAL in CEP is usually ___
> 30-40%
Typical age of hypereosinophilic syndrome
young middle aged males
Dx of hypereosinophilic sd
Unexplained eosinophilia >1500 for >6 mo or on 2 exams >1 mo apart
and/or
End-organ dysfunction due to eosinophils
Tx of HES
steroids
IFN-alpha
Chemotherapy
Hydroxyurea
Imatinib
Mepolizumab
3 phases of EGPA
Does not always progress and not all always present:
- asthmatic (8-10 years) with allergic rhinitis, atopy
- eosinophilic: peripheral and tissue eosinophilia (lung, GI skin)
- vasculitic - necrotizing vasculitis of small & medium vessels; extravascular granulomas- constitutional sx
Mononeuritis multiplex (foot drop) and asthma, think ___
EGPA
EGPA dx
4/6 criteria:
1. Asthma
2. Peripheral eos >10% or >1500
3. Paranasal sinus abnormalities
4. Mononeuropathy or polyneuropathy
5. Migratory pulmonary opacities (nodules, GGO, cavitation
6. Extravascular eos on biopsy
Serology in EGPA
pANCA, MPO 40-60% - more of the vasculitic phase
if ANCA negative – more eosinophilic phase
Tx EGPA
corticosteroids
Ritux
Azathioprine
MTX
Leflunomide
Mepolizumab
What is Five Factor Score for EGPA
Age >65
Cardiac involvement
Renal
GI
Absence of ENT involvement
(0-2 with 1 point/factor)
If FFS 2 or more, or organ infiltration, need stronger medications
Asteroid body
sarcoid
Treatment of refractory checkpoint inhibitor pneumonitis
Steroids –>
Infliximab or mycophenolate
