ILD Flashcards
HRCT patterns
1) UIP pattern:
- subpleural & basal predominant
- honeycombing
2) Probable UIP:
- subpleural and basal predominant (no subpleural sparing)
- reticular pattern with or without traction bronchiectasis/ bronchiolectasis
3) Indeterminate UIP:
- diffuse, no subpleural predominance
4) Alternative Dx:
Peribronchovascular with subpleural sparing (NSIP)
Perilymphatic (sarcoidosis)
Upper or mid lung (fibrotic HP, sarcoidosis, CTD-ILD)
Subpleural sparing (NSIP, smoking related)
Cysts
Mosaic attenuation (HP)
GGO (HP, smoking related, drug, exac)
profuse centrilobular micronodules (HP, smoking)
Consolidation
Pleural plaque (asbestosis)
Dilated oesophagus (CTD)
IPF
- Ix
- Mx
To be considered in >65, smoker
Ix:
1) HRCT findings of UIP pattern:
Traction bronchiectasis/ bronchiolectasis
Honeycombing
Pleuroprenchymal fibroelastosis (PPFE) seen in 6-10% of IPF→ rapid decline or PFT, pneumothorax, pneumomediastinum, poor survival
- to be repeated annually & when Sx worsen
2) PFT & 6MWT
- every 4-6/12
3) Consider lung Bx (either transbronchial lung cryotherapy TBLC or surgical) if Dx cannot be made from imaging
4) Consider BAL TRO other causes e.g. HP
5) CTD workup TRO other causes
6) MDT
Mx:
1) Antifibrotic
1.1) Pirfenidone
Dose: 267mg TDS for 7d, then 534mg TDS then 801mg TDS
CI in CrCl <30, Child Pugh C
ADR: GI (N,V,D), transaminitis, myalgia, headache
1.2) Nintedanib – dose given in IPR (100mg OD for 2w, then 100mg BD)
Dose: 150mg BD, 100mg BD in Child Pugh A
ADR: GI (N,V,D), blood (low plt, neut), neuro (neuropathy, headache)
2) Non-pharmacological
2.1) Smoking cessation
2.2) LTOT
2.3) Vax
2.4) Rehab
2.5) Nutrition
2.6) Lung transplant
3) Screen/ Mx of comorbidities:
3.1) Pulm HTN
3.2) OSA
3.3) GORD
3.4) Lung Ca
Mx of exacerbation: (but no robust evidence)
- High dose steroid
- Abx
Pleuroparenchymal Fibroelastosis (PPFE)
- Epi
- Causes
- Sx
- Ix
- Mx
Epi:
unknown
Pathophysio: Acute/subacute lung injury causing interstitial inflammation. Exact nature is unknown
Age: 40-70s. can also occur in children
F>M
Median survival 11y
Complication: pneumothorax/ pneumomediastinum
Causes:
1) Idiopathic
2) Post-transplant: bone marrow, lung, stem cell
3) autoimmune/ CTD
4) post-infection
5) Occupational exposure to asbestos/ aluminium
6) familial
Sx:
progressive SOB
cough
nonspecific chest discomfort and pleuritic pain
LOW
platythorax
Ix:
CT scan: upper zone pleural thickening/ fibrosis & volume loss
MDT
HPE
PFT: restrictive, reduced DLCO
ABG: increased A-a gradient
Mx: lung transplant
Autoantibody screening tests to be done in ILD
Core tests:
i) ANA
ii) ENA:
- SSA/Ro60, Ro52, SSB/La
- Scl70, RNP, Sm, centromere
iii) RF, Anti-CCP
iv) dsDNA
v) ANCA
vi) CK
Myositis Assoc Ab:
i) Ro-52; Anti-U1 RNP
ii) PM-Scl; Ku
Myositis Specific Ab:
i) Jo-1; OJ; EJ; PL-12; PL-7; MI-2
ii) SRP
iii) CADM140/MDA5
iv) NXP2
v) TIF1
vi) SAE
Pregnancy in ILD
- problem
- Mx
- Meds
Problem:
i) Higher miscarriage/ prem delivery/ IUGR
ii) Flare during preg
iii) Discont meds in preg
Mx:
i) Discuss with pt of risk & benefit
ii) Labour & delivery managed by O&G
iii) Timely regional anaesthesia during labour
Meds:
Safe in preg: steroid, Aza
Contraindicated in preg: MMF, Cyclophosphamide, Nintedanib, Pirfenidone
Holistic approach to ILD Mx
Systemic Sclerosis-ILD (SSc-ILD)
- B/ground
- Risk factors
- Ix
- Prognosis
- Rx
B/ground:
- Progressive & multiorgan (skin, lungs, GIT, MSK)
- ILD in >80%
- Classification:
a) Limited cutaneous (lcSSc): skin involvement distal to elbow & knees +/- face
b) Diffuse cutaneous (dcSSc): skin of trunk/ extremities
Risk factors:
- Male
- African American
- Diffuse subtype
- Anti-Scle-70 Ab +ve
- Nucleolar ANA
- Elevated CRP
- Baseline FVC<70%
- Baseline DLCO <55%
- >20% fibrosis on HRCT
Ix:
- Scl-70 (more prone at having progressive ILD),
- centromere (more assoc with pulm HTN),
- RNA polymerase Ab
Prognosis:
- ILD main COD, can be rapid progression or indolent
- Modified Rodnan Skin Score (mRSS): Measurement of skin thickness is used as a surrogate for disease activity, severity and mortality in patients with dcSSc
Rx:
Initial:
- MMF or
- Cyclophosphamide (CYC).
- Nintedanib
- Tocilizumab (anti-IL-6 inhibitor)
- Aza not popular sec to mixed results
*Steroids may cause renal crisis (usu pred>15mg, Sx: severe HTN, CCF, HTN encephalopathy) – to give ACEi
What are the types of CTD-ILD?
RA-ILD
Systemic sclerosis-ILD (SSc-ILD)
Idiopathic Inflammatory Myopathy-ILD (IIM-ILD)
Sjogren’s Syndrome
SLE
Mixed Connective Tissue Diseases (MCTD)
HRCT features suggestive of CTD-ILD
1) Anterior upper lobe sign
2) Exuberant honeycombing sign
3) Straight-edge sign
4) UIP pattern – honey combing & reticulation
5) NSIP pattern – GGO & reticulation
Common HRCT changes to specific ILDs:
RA: Usu UIP (honey combing & reticulation)
SSc: Usu NSIP (GGO & reticulation)
IIMs: overlapping NSIP and OP
Familial Lung Fibrosis
- b/ground
- manifestation
- Ix
Familial Lung Fibrosis
B/ground:
- to be considered when ≥2 family members in 1st degree relatives are affected either idiopathic or non-idiopathic
- potential cause: Telomere Syndrome
- worse survival
Manfestation:
- FHx of pulm fibrosis and/or bone marrow failure
- Premature greying (<25y)
- Heam: macrocytosis, low plt
- Liver derangement
- Defective wound healing
- Non-melanoma skin Ca
Ix: Genetic testing
General Ix, monitoring & Rx to be done in CTD-ILD
1) Rule out other causes e.g. Infection
Drug-induced
Malignancy
Idiopathic and other ILD
2) Lab:
RA: RF, anti-CCP
SSc: Scl-70, centromere, RNA polymerase Ab
IIM: Jo-1, PL-7 and PL-12 – strong assoc to ILD, MDA-5 (suggestive of amyopathic DM – rapid ILD progression)
Sjogren’s syndrome: SS-A, SS-B Ab
MCTD: RNP
3) HRCT
4) +/- Lung Bx
5) SpO2 at rest, exertion and night
6) ECG/ Echo: CAD/myocarditis/pericarditis common –> may cause SOB
7) Esophagram
8) Skin & muscle Bx
9) PFT:
- Restrictive pattern, reduced FVC
- Reduced DLCO (due to pulm vascular disease)
- Decreased maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) in IIMs
10) Monitoring:
- Initial evaluation: PFT within 3m, HRCT within 6m
- Mild disease: 6-monthly PFT for first 1-2y
- Mod-severe disease: 3-monthly PFT, HRCT yearly for first 3y
- ECHO: 1-2 yearly
- Ax side effects of Rx
11) Adjunctive Rx:
- LTOT: maintain SpO2 >88%
- GORD Rx sec to oesophageal dysfunction
- Pulmonary rehab
- Vax – flu, pneumococcal
- Palliative care – throughout the course of disease, not just when terminal
- Lung transplant
12) Pharmacological Rx:
Dosing in IPR:
MMF: max 1000mg BD
Nintedanib: 100mg OD for 2w, then 100mg BD
Aza: started with 50mg → 100mg → 125mg every 2w with repeat FBC, RP, LFT each time. T pred given as well for Sx control in weaning off doses: 20mg OD → 17.5mg → 15mg → 10mg every 2w until full Aza dose given.
Scoring system in ILD
GAP scoring: mortality in 3y for ILD IPF
Other scoring system: du Bois - for 1y mortality in IPF
RA-ILD
- b/ground
- risk factors
- Sx
- prognosis
- Ix
- Mx
B/ground:
- Lung involvement in ~80% of pts
- 20% may have lung Sx before joint Sx
Risk factors: older, smoking, male, RA disease score, anti-CCP high titre
Sx:
Systemic (LOW, fever, fatigue, myalgia)
Joint: polyarticular synovitis
Prognosis:
Median survival: 6-8y, 40% 5-yr mortality
Progression & exac common
Ix:
Bloods: RF, anti-CCP
ECHO +/- RH cath
PFT:
Reduced FVC, reduced DLCO in PH, FER <0.7% maybe seen
HRCT: usu UIP, sometime NSIP
Rx:
Not much phase 3 trials – mainly case series
Nintedanib for progressive fibrotic ILD
Idiopathic Inflammatory Myopathies (IIM)
- B/ground
- Types
- Risk factors
- Rx
- Prognosis
Background:
- Disorder of muscle weakness, rash & autoantibodies. ILD can occur prior to after Dx
Types:
i) Dermatomyositis (DM)
– with rash, but Amyopathic DM (ADM) usu had rash but no muscle weakness
ii) Polymyositis (PM)
iii) Antisynthetase syndrome (ASS)
– ILD, myositis, Raynaud’s, fevers, mechanic hands, arthritis
Risk factors: genetic (e.g.HLA-DRB1*03:01), black, female, MDA-5 Ab (assoc with rapid progressive ILD unresponsive to Rx)
Rx: No RCTs
Immunosuppressant & steroids are successful
Prognosis:
7x increase Ca risk (esp DM) – need screening
Jo-1 and Ro-52 more severe
Sjogren Syndrome
B/ground:
- second most common autoimmune disease after RA
- increased risk of lymphoma
- peak age: 50s
- American College of Rheumatology classification criteria in 2012: (≥2)
1) positive serum anti-SSA/Ro and/or anti-SSB/La (or positive rheumatoid factor and anti-nuclear antibodies at a dilution >1/320);
2) minor salivary gland biopsy exhibiting focal lymphocytic sialadenitis with a focus score >1/4 mm2
3) keratoconjunctivitis sicca with ocular staining score >3
Typical characteristics:
- Eye and mouth dryness
- Asthenia (lethargy)
- Arthralgia
- vasculitis, lung, renal or neurological
- Lymphocytic infiltration of the salivary glands
- Respi manifestations:
a) ILD (usu NSIP)
b) Tracheobronchial disease/ Airway (cough +++)
c) Pulmonary amyloidosis
d) Pulm lymphoma
e) PE
f) Pulm HTN
Ix:
i) Anti-Ro (SS-A) and Anti-La (SS-B) Ab
ii) Lung Bx
iii) Shirmer’s test <5 mm in 5 min
Rx: steroid
