Lung disease - ILD
CTDs are a relatively common cause of ILD, with a prevalence ranging from 7.5-33.3% of
total ILD cases (SSc > IIM > RA > others). NSIP and OP can coexist and superimpose on one
another.
ILD causes:
-IPF
-Drugs : amiodarone, nitrofurantoin, MTX, ICIs, bleomycin.
-Environmental: silica, asbestosis
-Rheumatologic
-Hypersensitivity pneumonitis
-Radiation
-Other: Langerhans histiocytosis, lymphangioleiomyomatosis, pulmonary alveolar
proteinosis, eosinophilic pneumonia
-Malignancy-associated
ILD patterns
IPF: UIP
RA: UIP > NSIP > OP
Sjögren: primary: NSIP, secondary: UIP. Both linked with LIP and small-airway disease.
IIM: NSIP or OP. UIP is rare.
SSc, MCTD: NSIP > UIP.
AAV: NSIP > UIP, but MPA more UIP.
UIP: IPF > RA > SSc (10%) > MPA
OP: IIM, GPA, PAN, RA, SLE, SjS, SSc, cryoglobulinemia, AS, Behçet.
DAD: IIM, MDA5, SLE.
LIP: mostly in Sjögren. Can be found in RA and SLE (rarer).
NSPI has a more subacute (rather than insidious) onset than UIP and a better prognosis. UIP
has the worst prognosis and OP the best (it’s usually GC-responsive).
The corresponding histopathologic entity to obliterative bronchiolitis is constrictive
bronchiolitis.
SSc, IIM, MCTD: HRCT at screening. In other diseases when symptoms or risk factors. The
follow-up with PFTs every 3-6months for the first 3-5yrs and every 6-12 months thereafter.
For RA and others, less often, 6-12 months for the first 1-2 years and the annually.
Mosaic attenuation: consisting of areas of hyperlucent lung adjacent to more normal-
appearing lucency areas → obstructive small airways disease.
ILDs have ↓DLco because they ↑ membrane thickness. Alveolar hemorrhage has ↑DLco
because free Hgb binds to CO. Mismatch of disproportionally low DLco comparing to FVC:
think of PAH.
GGO means that underlying bronchovascular bundles are still visible – if they’re not it’s a
consolidation.
Bronchiectasis is characterized radiographically by the dilation of the airways larger than the
accompanying bronchial artery.
, UIP
Patchy, heterogeneous process with fibrotic areas interposed with normal lung and is
notable for characteristic fibroblastic foci.
Histology: temporally heterogeneous appearance with alternating areas of normal
lung, patchy interstitial inflammation, fibroblast foci and honeycomb change. Interstitial
inflammation is usually sparse and consists of an alveolar septal infiltrate of lymphocytes,
plasma cells and histiocytes associated with hyperplasia of type 2 pneumocytes.
Radiology: a characteristic pattern of peripheral (subpleural), bibasilar reticular
opacities associated with architectural distortion, including honeycomb changes (cystic
spaces within clearly definable walls, ≥2 rows) and traction bronchiectasis. Honeycombing is
the progressive augmentation of traction bronchiectasis into cysts >3mm.
features of UIP that indicate an underlying SARD:
1) straight edge sign
2) exuberant honeycombing (>70% of the fibrotic regions)
3) the anterior upper lobe sign: concentration of fibrosis in the anterior
aspect of the upper lobe with relative sparing of the remaining upper lobe.
NSIP (cellular / fibrotic)
uniform, homogeneous pattern with variable degrees of inflammation (cellular NSIP) or
fibrosis (fibrotic NSIP) and a noted paucity of fibroblastic foci on pathologic examination.
Histology: expansion of alveolar septa by a variably dense lymphocytic (but not only)
infiltrate ± fibrosis. Focal areas of organizing pneumonia resembling the histopathologic
changes seen in OP are a common finding. Temporally homogenous.
Radiology: GGOs, irregular lines, consolidation, subpleural sparing. NSIP differs from
classical organizing pneumonia in that "OP-like" areas represent <10% of the cross-sectional
area of the lesional tissue and are overshadowed by the interstitial pneumonia. The fibrotic
changes in fibrotic NSIP have the same peripheral subpleural distribution as in UIP, but differ
in that they are more temporally homogeneous in contrast to the heterogeneous pattern of
UIP. They also present with traction bronchiectasis (that cellular NSIP doesn’t have), but
without architectural distortion. These observations raise the possibility that some patients
with fibrotic NSIP may in fact have UIP that is not fully appreciated in the lung biopsies or
the contrary.
The key features that UIP has, differentiating from fNSIP:
-Patchy involvement and fibrosis with by abrupt transitions resulting in a patchwork pattern
-Architectural distortion that included honeycomb change and/or interstitial scarring
-Fibroblast foci
-Temporal heterogeneity
OP (patchy / focal / diffuse)
Acute invasion, even with fever. Predominately involves the distal airways (acini and
respiratory bronchioles) where there are intraluminal plugs of inflammatory debris and mild
interstitial inflammation in the surrounding lung. It is a reversible inflammatory and
fibroproliferative process that does not disrupt the underlying lung architecture. Responds
well to GCs. Can coexist with and superimpose on NSIP.
Histology: excessive proliferation of granulation tissue (Masson bodies =intraluminal
tufts of granulation tissue), which consists of loose collagen-embedded fibroblasts and
myofibroblasts, involving alveolar ducts and alveoli, with or without bronchiolar intraluminal
polyps. Intraluminal plugs of granulation tissue may extend from one alveolus to the
adjacent one through the pores of Kohn, giving rise to the characteristic "butterfly" pattern.
Bronchiolar lesions likely reflect extension of intraluminal plugs of granulation tissue from
alveolar sacs and ducts to the bronchioles. While the pathologic lesion is predominantly
CTDs are a relatively common cause of ILD, with a prevalence ranging from 7.5-33.3% of
total ILD cases (SSc > IIM > RA > others). NSIP and OP can coexist and superimpose on one
another.
ILD causes:
-IPF
-Drugs : amiodarone, nitrofurantoin, MTX, ICIs, bleomycin.
-Environmental: silica, asbestosis
-Rheumatologic
-Hypersensitivity pneumonitis
-Radiation
-Other: Langerhans histiocytosis, lymphangioleiomyomatosis, pulmonary alveolar
proteinosis, eosinophilic pneumonia
-Malignancy-associated
ILD patterns
IPF: UIP
RA: UIP > NSIP > OP
Sjögren: primary: NSIP, secondary: UIP. Both linked with LIP and small-airway disease.
IIM: NSIP or OP. UIP is rare.
SSc, MCTD: NSIP > UIP.
AAV: NSIP > UIP, but MPA more UIP.
UIP: IPF > RA > SSc (10%) > MPA
OP: IIM, GPA, PAN, RA, SLE, SjS, SSc, cryoglobulinemia, AS, Behçet.
DAD: IIM, MDA5, SLE.
LIP: mostly in Sjögren. Can be found in RA and SLE (rarer).
NSPI has a more subacute (rather than insidious) onset than UIP and a better prognosis. UIP
has the worst prognosis and OP the best (it’s usually GC-responsive).
The corresponding histopathologic entity to obliterative bronchiolitis is constrictive
bronchiolitis.
SSc, IIM, MCTD: HRCT at screening. In other diseases when symptoms or risk factors. The
follow-up with PFTs every 3-6months for the first 3-5yrs and every 6-12 months thereafter.
For RA and others, less often, 6-12 months for the first 1-2 years and the annually.
Mosaic attenuation: consisting of areas of hyperlucent lung adjacent to more normal-
appearing lucency areas → obstructive small airways disease.
ILDs have ↓DLco because they ↑ membrane thickness. Alveolar hemorrhage has ↑DLco
because free Hgb binds to CO. Mismatch of disproportionally low DLco comparing to FVC:
think of PAH.
GGO means that underlying bronchovascular bundles are still visible – if they’re not it’s a
consolidation.
Bronchiectasis is characterized radiographically by the dilation of the airways larger than the
accompanying bronchial artery.
, UIP
Patchy, heterogeneous process with fibrotic areas interposed with normal lung and is
notable for characteristic fibroblastic foci.
Histology: temporally heterogeneous appearance with alternating areas of normal
lung, patchy interstitial inflammation, fibroblast foci and honeycomb change. Interstitial
inflammation is usually sparse and consists of an alveolar septal infiltrate of lymphocytes,
plasma cells and histiocytes associated with hyperplasia of type 2 pneumocytes.
Radiology: a characteristic pattern of peripheral (subpleural), bibasilar reticular
opacities associated with architectural distortion, including honeycomb changes (cystic
spaces within clearly definable walls, ≥2 rows) and traction bronchiectasis. Honeycombing is
the progressive augmentation of traction bronchiectasis into cysts >3mm.
features of UIP that indicate an underlying SARD:
1) straight edge sign
2) exuberant honeycombing (>70% of the fibrotic regions)
3) the anterior upper lobe sign: concentration of fibrosis in the anterior
aspect of the upper lobe with relative sparing of the remaining upper lobe.
NSIP (cellular / fibrotic)
uniform, homogeneous pattern with variable degrees of inflammation (cellular NSIP) or
fibrosis (fibrotic NSIP) and a noted paucity of fibroblastic foci on pathologic examination.
Histology: expansion of alveolar septa by a variably dense lymphocytic (but not only)
infiltrate ± fibrosis. Focal areas of organizing pneumonia resembling the histopathologic
changes seen in OP are a common finding. Temporally homogenous.
Radiology: GGOs, irregular lines, consolidation, subpleural sparing. NSIP differs from
classical organizing pneumonia in that "OP-like" areas represent <10% of the cross-sectional
area of the lesional tissue and are overshadowed by the interstitial pneumonia. The fibrotic
changes in fibrotic NSIP have the same peripheral subpleural distribution as in UIP, but differ
in that they are more temporally homogeneous in contrast to the heterogeneous pattern of
UIP. They also present with traction bronchiectasis (that cellular NSIP doesn’t have), but
without architectural distortion. These observations raise the possibility that some patients
with fibrotic NSIP may in fact have UIP that is not fully appreciated in the lung biopsies or
the contrary.
The key features that UIP has, differentiating from fNSIP:
-Patchy involvement and fibrosis with by abrupt transitions resulting in a patchwork pattern
-Architectural distortion that included honeycomb change and/or interstitial scarring
-Fibroblast foci
-Temporal heterogeneity
OP (patchy / focal / diffuse)
Acute invasion, even with fever. Predominately involves the distal airways (acini and
respiratory bronchioles) where there are intraluminal plugs of inflammatory debris and mild
interstitial inflammation in the surrounding lung. It is a reversible inflammatory and
fibroproliferative process that does not disrupt the underlying lung architecture. Responds
well to GCs. Can coexist with and superimpose on NSIP.
Histology: excessive proliferation of granulation tissue (Masson bodies =intraluminal
tufts of granulation tissue), which consists of loose collagen-embedded fibroblasts and
myofibroblasts, involving alveolar ducts and alveoli, with or without bronchiolar intraluminal
polyps. Intraluminal plugs of granulation tissue may extend from one alveolus to the
adjacent one through the pores of Kohn, giving rise to the characteristic "butterfly" pattern.
Bronchiolar lesions likely reflect extension of intraluminal plugs of granulation tissue from
alveolar sacs and ducts to the bronchioles. While the pathologic lesion is predominantly
