Download Rheumatological diseases are the common

“Rheumatological
diseases”
An
Immunological
threat for lung.
•
•
•
•
Dr. Jalal Mohsin Uddin
M.B.B.S
D.T.C.D
F.C.P.S (Pulmonology)
• What are
the
common
rheumatolo
gical
diseases
involving
the lung?
The five RDs most frequently associated
with pleuropulmonary disease
(1) rheumatoid arthritis (RA),
(2) systemic lupus erythematosus (SLE),
(3) progressive systemic sclerosis (PSS),
(4)polymyositis/dermatomyositis
(PM/DM), and
(5) Sjögren syndrome (SS).
Others include :
Mixed connective tissue disease (MCTD)
Ankylosing spondylitis
Behcet’s syndrome
Why lung is
involved in
rheumatolo
gical lung
diseases ?
• the lungs receive the entire
cardiac output of blood supply, so
that if there is an immune
problem or infectious problem
somewhere in the body, very often
the lung is affected. That would be
a general answer to the question
of why the lungs get involved so
frequently with rheumatologic
problems.
How a patient
with
rheumatological
diseases may
present to
pulmonologist ?
• May present with
• A) Original connective tissue disease
affecting the lung.
• B) Opportunistic pulmonary infection
• May be in those taking
immunosuppresive drugs or functionally
immunosupressed from underlying
disease.
• Any usual organism, also TB, nontuberculous mycobacteria, PCP, fungi,
cytomegalovirus etc may affect the
lung.
• C)Drug induced side effects ,eg.
Methotrexate, gold, penicillamine etc.
• D) New pulmonary pathology
• E)Unrelated to the original condition,
including pulmonary thromboembolic
disease.
What is the relative frequency of pleuropulmonary manifestations of
systemic rheumatologic disorders ?
--, not clinically important ; +, <5% ; ++,
5% to 25% ; +++, 25% to 50%, ++++,
>50 % incidence
RA
SLE
PM/D
M
Sjogren
SSc
syndrome
MCTD
Pleural disease
++
+++
--
+
--
++++
Pneumonitis
--
+
--
--
aspira +
tion
Alveolar haemorrhage
--
+
--
--
--
+
Interstitial pneumonia
++++
++
+++
+++
++++
+++
Pulmonary hypertension
+
++
+
--
++++
+++
Airway obstruction
++
--
--
+++
--
+
Bronchiectasis
+++
--
--
++
+
--
Respiratory muscle weakness
--
++
+
--
--
+
How Rheumatoid arthritis involve the
lung ?
• A study in patients, recently diagnosed with
rheumatoid arthritis found that
• 30% of patients reported respiratory symptoms (dyspnoea,
cough, wheeze),
• 20% of patients had physiological evidence of airflow
obstruction and
• 40% had reduced gas transfer.
• The prevalence of abnormalities found with high-resolution
CT was
• decreased attenuation in 67%,
• bronchiectasis in 35%
• bronchial wall thickening in 50%,
• ground glass opacification in 18%, and
• reticular changes in 12% of patients.
What is Rheumatoid nodule of lung ?
• It is the only pulmonary manifestation specific
to rheumatoid arthritis .
• Pulmonary rheumatoid nodule is rare ,
prevalence ranges from less than 0.4% in
radiological studies to 32% in lung biopsies of
patients with RA.
• They occur more frequently in male patients
with positive RF, smokers and those with
subcutaneous nodules. Sometimes may appear
before joint manifestation.
• They are typically benign and asymptomatic
but sometimes may lead to pleural effusion,
pneumothorax, bronchopleural fistula,
haemoptysis and secondary infection.
• Do not require specific treatment, may regress
spontaneously or may remain unchanged.
Who has rheumatoid nodule
in hand may have nodule in
lung.
How rheumatoid nodule
look radiologically ?
• Radiologically they present as
rounded, multiple nodules, and
more rarely as solitary pulmonary
nodule.
• They are preferentially located in
the middle and peripheral part of
upper lobe or pleural-based, with
a size ranging from millimeters to
7cm.
• Up to 50% may cavitate, and be
accompanied by an associated
pleural effusion, pneumothorax or
hydropneumothorax.
What is
Caplan's syndrome ?
• In 1953, Caplan described a characteristic
radiographic pattern in coal miners with
rheumatoid arthritis. It develops
especially in miners working in coal
mines and in persons exposed to silica
and asbestos. There is probably also a
genetic predisposition and smoking is
thought to be an aggravating factor.
•
•
•
•
Management
Exposure to coal dust must cease.
Smoking should cease.
After exclusion of TB, steroids are used.
Treatment of the RA will include diseasemodifying anti-rheumatic drugs
(DMARDs) at an early stage.
Can you identify
Caplan’s syndrome
radiologically ?
• CXRs show multiple welldefined rounded nodules,
which are about 0.5-2 cm in
diameter, distributed
throughout the lungs but
predominantly at the lung
periphery. CT scanning gives
a better picture of
cavitation.
What do you know
about RA-ILD?
UIP
• Interstitial lung disease (ILD) is a frequent extraarticular
manifestation of rheumatoid arthritis (RA).
• The majority of cases of RA-ILD occur in patients
between the ages of 50 and 60 years. More common in
male gender, smoker, positive RA factor and
longstanding RA to be risk factors for the development
of ILD.
• While the nonspecific interstitial pneumonia (NSIP)
pattern predominates in most forms of connective
tissue-associated ILD, but in RA-associated ILD (RAILD) the usual interstitial pneumonia (UIP) pattern is
more common .
UIP
NSIP
• High-resolution CT (HRCT) scans appear
accurate in identifying UIP pattern with
RA-ILD.
• UIP carrying the worst outlook and those
with non-specific interstitial pneumonia
(NSIP), COP and overlap syndromes (OS)
having better prognosis.
• HRCT assessment of disease extent also
predicts survival, with extensive disease
defined as >20% of lung affected on
HRCT.
• Though RA is often diagnosed before the
detection of ILD due to the presence of
articular disease, patients may present
de novo with isolated pulmonary
disease.
COP
A: NSIP pattern; HRCT scan demonstrating
the characteristic radiographic
appearance of NSIP with bilateral,
ground-glass opacities.
B: NSIP pattern; lung biopsy specimen
demonstrating a homogeneous cellular
infiltrate typical of NSIP pattern.
C: UIP pattern; HRCT scan demonstrating
the characteristic radiographic
appearance of a UIP pattern with
bibasilar, reticular abnormalities,
traction bronchiectasis, and
honeycombing.
D: UIP pattern; a lung biopsy specimen
demonstrating areas of established
fibrosis next to normal lung and focal
fibroblastic activity (fibroblast foci)
typical of UIP pattern (arrows).
Although honeycombing is not seen on
this view, the image demonstrates the
classic “temporal heterogeneity” of UIP
pattern.
Proposed algorithm for
the evaluation and
management of suspected
patients with RA-ILD.
• Patients with suspected RAILD should be screened
annually for the presence of
ILD with a history and a
physical examination. In
suspected cases of ILD,
additional testing with PFTs
and HRCT scanning is
indicated. In the absence of
a definitive radiographic
pattern, surgical lung biopsy
should be considered.
Is Anti-rheumatic drug is responsible for
detoriation of ILD?
• Methotrexate (MTX) has been
associated with pneumonitis in patients
with RA.
• It is difficult to predict which patients
may develop MTX pneumonitis.
• Patients are most likely to develop
pneumonitis within the first 6 months
of MTX therapy and prognosis tends to
be worse in this group, with a case
fatality rate of 20%.
• MTX has not been shown to accelerate
the progression of underlying RA-ILD but
the increased risk of pneumonitis.
• It may not always be the safest first-line
disease-modifying anti-rheumatic drug
(DMARD) in such patients.
• It’s thought that re-challenging patients with methotrexate
may somehow cause a stronger secondary response.
• In making a diagnosis of methotrexate lung injury, you have
major and minor criteria.
• The three major criteria are:
• Hypersensitivity pneumonitis by histopathologic examination
• Radiologic evidence of pulmonary interstitial or alveolar
infiltrates
• Blood and sputum cultures negative for organisms
• The minor criteria include:
• Shortness of breath
• A nonproductive cough
• O2 saturation ≤90% on room air at initial evaluation
• DLCO ≤70% of that predicted for age
• WBC ≤15,000 per mm3
• Diagnosis is made by either major criteria 1 by itself, or
criteria 2 and 3 together with three of the minor criteria.
• Leflunomide has also been reported to cause
pneumonitis, although this appears to occur much
more frequently in Japanese and Korean patients, but
patients with a history of MTX pneumonitis are also at
increased risk of pneumonitis with leflunomide.
• There is some evidence that several anti-tumour
necrosis factor (TNF) agents used in the treatment of
RA may accelerate progression of ILD. There have been
reports of patients with mild ILD started on etanercept,
infliximab and adalimumab who have developed
rapidly progressive and often fatal pulmonary
fibrosis.
Patients with RA-ILD appear to fall into three broad
categories, and this distinction is important when
deciding whom and how to treat ?
• The first group are those with no
symptoms of lung disease in whom
the discovery of ILD has been
incidental and based on clinical or
radiological examination, confirmed
by HRCT. If these patients remain
asymptomatic and have no evidence
of progression with time as evidenced
by stable PFTs, then no specific
therapy for their lung disease appears
necessary. The use of MTX in this
group does not appear to be
specifically contraindicated.
Second group :
• Patients with gradually increasing symptoms of
dyspnoea in the presence of proven
RA-ILD (UIP pattern) require a more targeted approach.
• Many of these will have evidence of steady deterioration in their
pulmonary function and/or radiological appearances.
• Such patients justify treatment for their pulmonary disease, in
addition to single or combined DMARD therapy for articular features.
• Mycophenolate (2 g daily), with or without N-acetylcysteine (600 mg
tds), has been advocated.
• Cyclophosphamide (2 mg/kg/day orally) is initiated in conjunction
with lower-dose prednisone (0.25 mg/kg/day) for steroid
nonresponders. If they respond, therapy is continued for 18 months
to 2 years at which point the medical regimen may be reconsidered
or therapy can continue indefinitely. Appropriately selected nonresponders are referred for lung transplantation.
Third group :
• The third group comprises those RA patients with rapidly progressive
ILD. These patients are at risk of imminent respiratory failure and
many will have extensive UIP on HRCT.
• Six cycles of intravenous cyclophosphamide (15 mg/kg) with
methylprednisone (10 mg/kg) at 3–4 weekly intervals has proved
effective .
• Clinical experience suggests those patients who improve with this
regime might then be maintained with mycophenolate.
• The presence of ILD may also influence the choice of DMARD and
biologic therapy in RA. The use of MTX in combination with anti-TNF
agents should probably be avoided in the presence of ILD.
Role of prednisolone in RA-ILD
• If characteristics of NSIP or BOOP
predominate the radiologic appearance with
ground glass infiltrates on HRCT,
glucocorticoids alone may be effective . We
NSIP
should follow a standardized protocol set by
Healthy
Lazor et al. in which patients received
0.75 mg/kg/day prednisone during the initial
four weeks of treatment, then 0.5 mg/kg/day
for the next four weeks, then 20 mg/day for
four weeks tapering to 10 mg/day for the
NSIP lacks the extensive fibrosis with
next 6 weeks, and then 5 mg/day for 6 weeks honeycombing. Ground glass opacity is
the predominant pattern.
.
• A definitive response to treatment is defined
as a 10% improvement in the FVC or 15%
improvement in the DLCO at 12 weeks . We
should continue therapy even if there is a
marginal degree of improvement (5–10% in
FVC or 10–15% in DLCO) .
steroid sparing therapy
• If the patient meets criteria for
improvement, we check thiopurine
methyltransferase (TPMT) activity levels
and if normal initiate steroid sparing
therapy with azathioprine 50 mg daily
gradually increasing the dose to 23 mg/kg/day .
• If TPMT activity is decreased,
cyclosporine is substituted at a dose of
2.5 mg/kg/day divided twice daily .
• If the FVC and DLCO remain stable with
quarterly PFT assessments over a twoyear period, we consider this evidence
that progression of disease has been
halted, at which time it may be
reasonable to reassess the medical
regimen .
COP/BOOP
There are patchy non-segmental
consolidations in a subpleural and
peripheral distribution.
Treatment of RA-ILD Exacerbation
• An ILD exacerbation is generally defined as rapidly deteriorating
respiratory symptoms within a 30-day period with evidence of new
infiltrates (usually new ground glass opacities) and exclusion of an
identifiable cause.
• If the underlying histopathology is NSIP or BOOP, there is a
reasonable probability for a sustained clinical response to
glucocorticoid treatment alone or in conjunction with other
immunosuppressive agents.
• Ground glass infiltrates on the background of UIP often herald the
development of diffuse alveolar damage, and the ensuing
mortality approaches 80–100%.
• Generally treatment is initiate with IV methylprednisolone at a
dose of 1 mg/kg/day for 3 days followed by oral prednisolone
1 mg/kg/day.
• If there is no evidence of improvement in paO2/FiO2ratio or
oxygen saturation rescue therapy with cyclophosphamide
(500–750 mg/m2) may be considered .
• Other regimens have employed cyclosporine 3 mg/kg/day
or tacrolimus 3 mg/kg/day in divided doses in patients
unresponsive to cyclophosphamide with some success in
isolated case reports .
• If the patient progresses to the point of requiring
ventilatory support, consideration should be given to
noninvasive ventilation, and/or lower PEEP settiing .
Are you worried about bronchiectasis
with rheumatod arthritis ?
•
Bronchiectasis (BR) occurs in about 3%
of patients with rheumatoid arthritis
(RA).
• Patients with rheumatoid arthritis and
bronchiectasis have worse obstructive
airways disease, increased susceptibility
to recurrent lower respiratory tract
infections, faster lung function decline
and higher mortality compared with
subjects with bronchiectasis alone.
What is the prognosis of Obliterative
 Obliterative bronchiolitis (also termed
bronchiolitis ?
bronchiolitis obliterans / follicular bronchiolitis




/constrictive bronchiolitis) is a type of
bronchiolitis and refers to bronchiolar
inflammation / sub mucosal peribronchial fibrosis
associated with luminal occlusion / stenosis.
These diseases are usually seen in patients with
positive rheumatoid factor and active joint
disease.
The symptoms are characterized by dyspnea and
nonproductive cough.
Although chest radiograph is generally normal,
computed tomography may show areas of air
trapping, small nodular opacities in centrilobular
distribution (follicular bronchiolitis and
bronchiolitis obliterans), patchy areas of low
attenuation (bronchiolitis obliterans), and
peribronchial thickening (follicular bronchiolitis
and bronchiolitis obliterans). PFTs reveal airflow
obstruction.
Presents with rapid-onset dyspnoea and dry
cough. Fever is uncommon.
the mosaic attenuation pattern
caused by the airway
obstruction is accentuated
during forced expiration due to
air trapping in areas with
bronchial obstruction.
• rheumatoid-arthritis-related
constrictive bronchiolitis is not rare ,
but continues to be poorly
responsive to therapy and has a
poor prognosis.
• In a 2009 report from France of 25
individuals with rheumatoid arthritis
and obliterative bronchiolitis, most
had severe airflow obstruction, often
with an FEV1 of less than one liter,
and did not improve when treated
with corticosteroids .
• The prognosis was poor: chronic
respiratory failure occurred in 40%
of patients and four died.
Are you worried about pleural effusion of rheumatoid
arthritis ?
Pleural effusion usually occurs in patients previously
diagnosed with rheumatoid arthritis, but it can also occur
concurrently with or before the development of the joint
manifestations of the disease .
 Pleural effusion is common in middle-aged men with RA and
positive rheumatoid factor (RF). occurring in 2-3% of
patients. It has features of an exudate and a high RF titer.
Underlying lung pathology is common.
 Rarely, RPE has features of a sterile empyematous exudate
with high lipids (cholesterol crystal) and lactate
dehydrogenase, and very low glucose and pH levels. This
type of effusion eventually leads to fibrothorax and lung
restriction. Superimposed infective empyema often
complicates RPE.
Pleural effusions in rheumatoid arthritis are usually small,
unilateral (25% bilateral), and asymptomatic.
Histopathological findings in pleural biopsy
• Light microscopy reveals replacement of normal
cells lining the pleura mesothelial cells by a layer of
pseudostratified epithelioid cells, multinucleated
giant macrophages, and necrotic material.
• Diagnosis relies on the characteristic cytopathology
of the exudative pleural fluid, which contains
elongated and giant multinucleated macrophages • Pleural and pericardial
effusions secondary to
in a sea of amorphous granular material.
serositis were found in a
• The absence of mesothelial cells is also
25-year-old woman with
characteristic . These findings are highly specific for
rheumatoid arthritis. The
rheumatoid pleuritis.
transverse CT image after
administration of
• Generally RPE is small and resolves spontaneously
intravenous contrast
but symptomatic RPE may require thoracocentesis.
demonstrates
Steroids are the mainstay of treatment . Oral,
enhancement of the
parenteral, and intrapleural corticosteroids,
pericardium (arrows),
pleurodesis and decortication, have been used for
which is typically seen
the treatment of sterile RPE. Infected empyema is
with exudative effusions.
treated with drainage and antibiotics.
• Arteritis:
– Arteritis of the pulmonary artery and
lung is rare; signs of systemic
vasculitis are usually present.
• Infection:
– Respiratory infections account for 1520% of deaths in rheumatoid patients.
• Other diseases:
•
– Apical emphysematous bullae can be
seen, with emphysema and in people
who smoke, but can be similar to
what’s seen in ankylosing spondylitis,
making it difficult to differentiate.
– Thoracic cage immobility causing
restrictive lung disease.
– Primary pulmonary hypertension
(rare); secondary pulmonary
hypertension (due to ILD) is more
common
– Lung cancer
Cricoarytenoid arthritis usually
involves hoarseness, trouble
swallowing, and obvious speaking or
breathing problems.
• Shrinking lung is extremely rare.
Cricoarytenoid rheumatoid arthritis A, Axial 3mm-thick contrast-enhanced CT demonstrates
an aggressive, erosive mass of the posterior
larynx (arrow). The mass has lower attenuation
centrally, and the borders are ill defined. The
thyroarytenoid gap is widened, and the mass
extends posteriorly toward the right pyriform
sinus. B, CT with bone algorithm at a slightly
lower level shows erosion of the cricoid
cartilage (arrows). The scattered locules of air
are from a recent tracheostomy.
How lungs may be affected by SLE?
• Although severe parenchymal lung disease is uncommon, pulmonary
complications of SLE are protean and include
• acute lupus pneumonitis,
• diaphragmatic dysfunction and shrinking lung syndrome,
• cavitating pulmonary nodules,
• pulmonary hypertension,
• pulmonary vasculitis,
• pulmonary embolism (often due to circulating
anticardiolipin antibodies),
• alveolar haemorrhage (reflecting diffuse endothelial injury),
• chronic interstitial pneumonitis,
• bronchiolitis obliterans (with or without organising pneumonia),and
• opportunistic pulmonary infections or drug toxicity from
immunosuppressive therapy.
Pleural disease, is it common in SLE ?
• The most common thoracic manifestation of SLE is pleuritis.
• Pleuritic pain is present in 45–60% of patients and may occur with or
without a pleural effusion.
• Clinically apparent pleural effusions have been reported in up to 50% of
patients with SLE and may be found in up to 93% of cases at necropsy.
• Effusions are usually bilateral but may be unilateral, equally distributed
between the left and right hemithoraces.
• They are invariably exudative with higher glucose and lower lactate
dehydrogenase levels than those found in rheumatoid arthritis.
• Antinuclear antibody (ANA), anti-DNA antibodies, and LE cells have been
found in the pleural fluid. LE cells appear to be relatively specific.
• Pleural biopsies have rarely been performed in SLE and the findings are
non-specific, revealing lymphocytic and plasma cell infiltration, fibrosis, and
fibrinous pleuritis. They are indicated primarily to exclude alternative
aetiologies.
• Thoracoscopy has revealed nodules on the
visceral pleura and immunofluorescence of
biopsy samples of these nodules revealed
immunoglobulin deposits.
Treatment of
pleural effusion :
• Treatment of pleural disease depends
on the severity of symptoms.
• Small asymptomatic effusions may not
require specific treatment. Nonsteroidal anti-inflammatory agents may
be effective for mildly symptomatic
pleurisy.
• For more severe disease or in patients
already receiving corticosteroids,
increasing doses of corticosteroids are
frequently required.
• Long term management may involve
the use of antimalarial drugs such as
hydroxychloroquine.
• Invasive procedures such as chest tube
drainage or pleurodesis are rarely
required.
Chest radiograph showing left pleural
effusion in a 50 year old man with
arthritis, fever, and high titre anti-DNA.
Thoracentesis demonstrated typical LE
cells
Chronic interstitial pneumonitis (CIP)
Clinically significant chronic interstitial pneumonitis (CIP) complicates
SLE in 3–13% of patients but is rarely severe.
Asymptomatic involvement is more common and abnormalities in
pulmonary function tests have been cited in up to two thirds of
patients with SLE in some studies.
Progression of recurrent acute lupus pneumonitis to CIP probably occurs
since there are examples of persistent disease following acute onset,
and the mean age of onset of acute disease (38 years) is earlier than
that for chronic disease (46 years).
Chest radiographic abnormalities consistent with CIP have been cited in
6–24% of unselected patients with SLE.
Subclinical CIP may be common, diagnosis depending on the sensitivity
of the diagnostic tests used, and the long term significance of this has
not been elucidated. However, symptomatic CIP is rarely an early or
dominant feature of SLE and severe pulmonary fibrosis is rare .
• Histological features of CIP complicating SLE are nonspecific and include varying degrees of chronic
inflammatory cell infiltrates, peribronchial lymphoid
hyperplasia, interstitial fibrosis, and hyperplasia of type
II pneumocytes. An association between anti-SS-A
antibodies and chronic lupus pneumonitis was
suggested in one study in which 81% of patients with
lupus pneumonitis had anti-SS-A (Ro) antibodies .
• Progressive severe CIP rarely complicates SLE but may
be seen in a subset of patients with SLE in the context
of overlap syndrome.
• Chronic interstitial pneumonia in
a 35 year old woman with SLE.
HRCT scan shows extensive
ground glass opacities admixed
with coarse linear bands and
honeycomb cysts. Open lung
biopsy confirmed the diagnosis.
Ground glass opacities
represented a mixture of fibrosis
and interstitial mononuclear cell
infiltrates. Treatment with
corticosteroids, azathioprine,
and later cyclophosphamide
failed and she subsequently
underwent a single lung
transplantation.
• Data evaluating treatment are
sparse. Corticosteroids,
immunosuppressive, or cytotoxic
agents may be efficacious, but
therapeutic trials are lacking.
Acute lupus
pneumonitis
• Acute lupus pneumonitis presenting as
cough, dyspnoea, pleuritic pain,
hypoxaemia and fever, occurs in 1–4% of
patients with SLE
• Chest radiographs reveal infiltrates which
may be unilateral or bilateral .
• Histological features are non-specific
and include alveolar wall damage and
necrosis, inflammatory cell infiltration,
oedema, haemorrhage, and hyaline
membranes.
• Favourable responses to corticosteroids
are achieved in most patients but the
course may be fulminant and
occasionally fatal. Immunosuppressive or
cytotoxic agents are reserved for
corticosteroid-recalcitrant patients.
A) Acute lupus pneumonitis in a 45
year old man. He was treated with
corticosteroids and a follow up
chest radiograph (B) at four weeks
revealed considerable
improvement.
Acute alveolar haemorrhage
• Pulmonary haemorrhage is
a rare but potentially
catastrophic complication of
SLE.
• Mortality has ranged from
50% to 90%.
• Clinical features are nonspecific but diffuse alveolar
infiltrates, hypoxaemia,
dyspnoea, and anaemia are
characteristic .
• Some of these features
may be lacking with minor
episodes.
Acute alveolar haemorrhage. Chest radiograph
showing extensive bilateral alveolar infiltrates
in a 22 year old woman with SLE, haemoptysis,
and anaemia.
Alveolar haemorrhage
• Alveolar haemorrhage usually occurs in
patients with a known history of SLE, higher
titres of circulating anti-DNA antibody, and
active extrapulmonary disease.
• In up to 20% of cases alveolar haemorrhage
may be the initial clinical manifestation of
SLE.
• Similar to other pulmonary haemorrhage
• Alveolar haemorrhagic
syndromes, glomerulonephritis is often
infiltrate in HRCT of chest.
present in SLE associated alveolar
haemorrhage.
• Lung biopsy specimens demonstrate
extensive haemorrhage within alveolar
spaces and “capillaritis”; these features are
non-specific.Deposits of IgG, C3, or
immune complexes have been found in up
to 50% of patients with alveolar
haemorrhage complicating SLE.
• Fibreoptic bronchoscopy with bronchoalveolar lavage
(BAL) and transbronchial lung biopsies can be
performed with minimal morbidity and is usually
adequate for the diagnosis of alveolar haemorrhage.
The presence of gross blood in the airways,
serosanguinous BAL fluid, haemosiderin laden
macrophages, absence of purulent sputum, and lack of
infectious organisms by appropriate stains strongly
support the diagnosis of alveolar haemorrhage.
• The treatment of choice is high dose steroids with or
without cyclophosphamide; plasmapheresis has been
used with anecdotal reports of success. Plasmapheresis
should be reserved for patients with severe alveolar
haemorrhage refractory to corticosteroids and
cytotoxic agents.
Pulmonary vascular disease
• ACUTE REVERSIBLE HYPOXAEMIA SYNDROME
• The clinical picture consists of hypoxaemia with associated
diffusion abnormalities due to an occlusive vasculopathy.
• There was no association with diffuse parenchymal disease.
The combination of activated endothelium and
complement activation leads to neutrophil sludging.
• Most cases respond to high dose corticosteroids. Lower
dose of corticosteroids in combination with high dose
aspirin may improve the pulmonary manifestations but may
not be sufficient to control the systemic activity of the
disease.
Vasculitis and pulmonary hypertension
•
•
•
•
•
•
•
Descriptions of primary pulmonary vascular
disease in the absence of parenchymal disease
are uncommon.
Raynaud's phenomenon is present in 75% of
cases.
multiple factors may be responsible for
pulmonary hypertension including pulmonary
vasculitis, thrombosis, and pulmonary artery
vasoconstriction.
The overall prognosis for patients with SLE and
pulmonary hypertension is poor with two year
mortality exceeding 50%.
Treatment is similar to that used in primary
pulmonary hypertension with vasodilators
being the mainstay of treatment.
Some authors have advocated the use of
corticosteroids with anecdotal reports of
success.
A recent report advocated the use of
combination treatment with
immunosuppression, anticoagulation, and
vasodilator therapy.
Chest radiograph from a woman with
severe pulmonary hypertension
(pulmonary artery pressure 120/60).
Note the prominent pulmonary arteries
bilaterally with straightening of the left
heart border and attenuation of the
peripheral vessels.
• Lupus anticoagulant has been demonstrated in patients
with SLE and is associated with an increased risk of
intravascular thrombosis. Acute and chronic pulmonary
emboli are well recognised complications of the
anticardiolipin antibody.
• patients with SLE anticardiolipin antibodies of IgG or IgM
isotype were associated with an increased prevalence of
thrombosis compared with patients with negative titres .
• Life long anticoagulation may be warranted in patients with
recurrent thromboembolic disease . In addition, intensive
treatment with corticosteroids or immunosuppressive
agents may be required when anticoagulation alone fails to
control thrombosis.
Airway disease
• Bronchiolar disorders rarely
complicate SLE. Abnormalities in
pulmonary function tests have
been detected in up to two thirds
of patients with SLE, even in the
presence of normal chest
radiographs, but severe airways
obstruction is rare.
• A few cases of cryptogenic
organising pneumonia (COP)
complicating SLE have been
described.
• corticosteroids are preferable as
initial treatment, with
immunosuppressive or cytotoxic
agents being reserved for patients
who fail to respond or are
intolerant of corticosteroids.
• HRCT scans can be useful to aid
diagnosis
(A) Inspiratory HRCT scan of a 43 year old
woman with SLE and obliterative
bronchiolitis. Faint areas of ground glass
opacity are apparent. (B) Expiratory HRCT
scan in the same subject with accentuation
of the mosaic pattern of ground glass opacity.
Diaphragmatic dysfunction
• Diaphragmatic dysfunction or “the shrinking lung syndrome”
is characterised by dyspnoea, which may be progressive in
nature, and the radiological findings of small lung volumes
and basilar atelectasis.
• It can be difficult to differentiate respiratory muscle
weakness from primary parenchymal disease or pleural
causes of low lung volumes.
• The best means of determining the cause of low lung volumes
is with the use of oesophageal and gastric pressure
measurements, phrenic nerve stimulation, or diaphragmatic
electromyography.
• True incidence of diaphragmatic dysfunction is not known.
Furthermore, the picture can be clouded by the use of
systemic corticosteroids which can lead to muscle weakness.
• Improvement has been reported in individual cases with the
use of corticosteroids, inhaled β agonists, and theophylline.
• A, Chest radiograph from a
patient with systemic
lupus erythematosus
shows marked elevation of
both hemidiaphragms, in
keeping with “the
shrinking lung syndrome.”
B, On a CT scan from the
same patient as in A,
linear abnormalities are
seen that denote
subsegmental atelectasis
resulting from regional
hypoventilation (due to
diaphragmatic weakness).
The heart is enlarged.
Systemic sclerosis and pulmonary disease :
• Evidence of pulmonary disease is found in over 80
percent of patients with systemic sclerosis (SSc).
• Pulmonary involvement is second in frequency only to
esophageal involvement as a visceral complication of
SSc and has surpassed renal involvement as the most
common cause of death .
• Interstitial lung disease (ILD) and pulmonary vascular
disease, particularly pulmonary arterial hypertension
(PAH), are the most frequent major types of lung
involvement.
• Affected patients have a worse prognosis than patients
with SSc who are free of pulmonary involvement.
Quantification of lung involvement :
• Patients with diffuse cutaneous sysemic
sclerosis(dcSSc) are at an increased risk of developing
ILD early in the course of their disease;
• Clinically significant ILD may also occur in patients with
limited cutaneous systemic sclerosis (lcSSc).
• The presence of nucleolar autoantibodies such as
Th/To, and less commonly anti-Scl-70 autoantibodies,
in patients with lcSSc are associated with increased risk
of ILD.
• Patients with lcSSc often develop PAH late in the
course of the disease with or without associated ILD.
What is SILD ?
• About two thirds of patients suffering from SSc
develop scleroderma ILD (SILD) .
• Currently, SILD is the leading cause of death in
SSc patients, due to pulmonary fibrosis with or
without PH. The mortality rate from SILD is about
40% within 10 years after the onset of the
disease
• In systemic sclerosis the most frequently
occurring pattern of fibrosis is one called nonspecific interstitial pneumonia (NSIP).
Do you know about scelroderma sine
scelroderma ?
• Pulmonary disease can even occur in SSc with
no skin involvement (an entity known as
scleroderma sine scleroderma) . These
patients can be misclassified as having
idiopathic ILD and the presence of
telangiectasias, Raynaud’s phenomena, reflux
or pericardial effusions; a nucleolarantinuclear antibody test should alert the
clinician to the possibility of scleroderma sine
scleroderma .
Fate of ILD related to Systemic
sclerosis :
• In the majority of individuals with systemic sclerosis,
lung fibrosis is limited in extent, and only causes
symptoms when individuals really exert themselves. In
these individuals the fibrosis tends to remain stable
over time and does not require specific treatment.
• However, in approximately one out of ten cases, lung
fibrosis is more severe and/or has a tendency to
worsen with time, because of continued development
of scar tissue in the lungs.
• When this is the case, treatment to prevent fibrosis is
required. Only in a very small number of individuals
does lung fibrosis progress despite treatment.
• There are four roles of imaging in scleroderma
interstitial lung disease: 1) detection of lung
involvement, 2) identification of patients likely
to respond to treatment, 3) assessment of
treatment efficacy, and 4) exclusion of other
significant diseases to include PH and cardiac
and esophageal abnormalities.
• HRCT has become an important part of the routine
evaluation of SILD. Classically, the disease affects
juxtapleural, posterior, and basilar portions of the
lungs, with initially subtle alterations of increased GGO,
defined as increased lung attenuation in the absence of
architectural distortion, as well as accentuated reticular
markings that may progress to pulmonary fibrosis,
defined as architectural distortion with reticular
intralobular interstitial thickening, traction
bronchiectasis and bronchiolectasis, and honeycomb
cystic change . These hallmark CT features of SILD are
similar to those of idiopathic, nonspecific interstitial
pneumonitis (NSIP).
• Coronal and sagittal chest
CT reconstructions (lung
window) demonstrate the
classic appearance of
scleroderma interstitial
lung disease in patients
with progressive disease,
showing extensive
architectural distortion
due to progressive
pulmonary fibrosis (a and
b)
• Esophageal dilatation
with retained debris is
an early and frequent
manifestation of
scleroderma and may
help differentiate
interstitial lung disease
due to connective tissue
disease from that of
other etiologies.
• Honeycomb cystic change is typically a marker
for usual interstitial pneumonia (UIP) and
pulmonary fibrosis , If these findings are
prominent in HRCT, it suggest that patients
with SILD disease may have a mixture (or
overlap) of UIP and NSIP patterns.
Treatment
• The most commonly used treatment for the lungs is a combination of low dose
steroids (usually 10 mg once daily) together with an immunosuppressant drug.
The immunosuppressants that are most frequently used for systemic sclerosis, are
azathioprine and mycophenolate. These immunosuppressants reduce the
overactivity of the immune system which plays a crucial part in the development of
irreversible lung scarring.
• In individuals with extensive or rapidly worsening lung fibrosis, intravenous
treatment (by drip infusion) with cyclophosphamide may be used.
Cyclophosphamide is also an immunosuppressant but when used intravenously it
acts more quickly than other immunosuppressant medications.
•
Treatment of lung fibrosis needs to be continued for as long as there is evidence of
on-going inflammatory activity due to systemic sclerosis. It is usually possible to
gradually reduce and stop treatment once the lung disease is no longer active. It is
important to realise , that this process of waiting for inflammatory activity to
subside and then gradually reducing and stopping treatment may take several
years.
PAH and SSc
• Epoprostenol, a synthetic prostacyclin analogue that elicits
potent vasodilatory, antithrombotic and inotropic effects, In a
12-week trial, epoprostenol given by continuous ambulatory
infusion improved exercise capacity and hemodynamic
characteristics in SSc-associated PAH.
• Randomized, placebo-controlled intervention trials
demonstrated that bosentan not only prevented the
deterioration in 6-minute walking distance and significantly
improved symptoms in SSc patients with advanced PAH, but
also reduced the risk of clinical worsening at 24 weeks,
suggesting that it may actually slow the progression of the
disease.Based on this short-term clinical experience,
bosentan recently became the first drug to be approved by
the Food and Drug Administration specifically for the
treatment of SSc.
Polymyositis/dermatomyositis with
pulmonary manifestation :
• on new PM and DM patients, a recent study
found that as many as two-thirds had signs of
interstitial lung disease, even though all the
patients were in early stages of myositis. PM and
DM patients seem to have about the same risk,
and the disease is rarely associated with
inclusion-body myositis. Recent studies show that
patients with amyopathic dermatomyositis
(dermatomyositis without the muscle symptoms)
are also at risk for lung disease.
• There are ways that physicians can predict the
likelihood of myositis patients developing
interstitial lung disease. Patients with anti-Jo1
antibodies are thought to be at a much higher
risk, maybe as high as 70 percent.
• Detecting the presence of lung disease sooner
rather than when symptoms are well established
is very important because appropriate treatment
may prevent the disease from becoming chronic.
• Difficulty swallowing. If the muscles in your esophagus
are affected, you may have problems swallowing
(dysphagia), which in turn may cause weight loss and
malnutrition.
• Aspiration pneumonia. Difficulty swallowing may also
cause you to breathe food or liquids, including saliva,
into your lungs (aspiration), which can lead to
pneumonia.
• Breathing problems. If your chest muscles are affected
by the disease, you may experience breathing
problems, such as shortness of breath or, in severe
cases, respiratory failure.
• most common is nonspecific
interstitial pneumonia. The
prognosis of interstitial lung
disease associated with
polymyositis is better than that of
idiopathic pulmonary fibrosis,
since most patients respond to
treatment with corticosteroids
and immunosuppressants.
• High-resolution computed
tomography showing a bilateral
interstitial pattern, with septal
enlargement, areas of ground
glass opacity, reticulation, and
traction bronchiectasis with
predominance in the lower
lobes.
• Tacrolimus led to stabilization or improvement
in four of five anti-Jo1 antibody-positive
patients with polymyositis. These
observations were confirmed in a larger
patient cohort of 13 patients.
• Tumor necrosis factor α (TNF-α) inhibitors
have also been mentioned as promising
agents for treatment of both myositis and
interstitial lung disease.
Sjögren syndrome (SS)
• Respiratory complications of SS include airway
mucosal dryness (also known as xerotrachea),
a variety of interstitial lung diseases (ILDs),
non-Hodgkin lymphomas, pleural thickening
or effusion, and, rarely, thromboembolic
disease or pulmonary hypertension.
• Interstitial lung disease in primary Sjögren syndrome usually
present with dyspnea and cough.
• Chest radiographs demonstrated bilateral infiltrates, and highresolution CT revealed abnormalities of various types
including ground-glass, consolidation, reticular, and nodular
opacities.
• The major histopathologic patterns included nonspecific
interstitial pneumonia (NSIP) , organizing pneumonia (OP) ,
usual interstitial pneumonia (UIP) , lymphocytic interstitial
pneumonia , primary pulmonary lymphoma , and diffuse
interstitial amyloidosis .
• Treatment commonly included prednisone with or without
another immunosuppressive agent. Except UIP pattern, in
other histological pattern, prognosis is better.
• Lymphocytic interstitial
pneumonia in Sjögren’s
syndrome. HRCT scan
demonstrates bilateral thinwalled cystic lesions in a
random distribution. Also
noted are small foci of
ground-glass attenuation
and a few linear opacities.
More extensive areas of
ground-glass attenuation
were present in the lower
lung zones.
Mixed connective tissue disease
• Pulmonary involvement is a common complication of
mixed CTD. Nearly 80% of the people with mixed
connective tissue disease have some involvement of
the lungs. Pleuritis, ILD and PHT are relatively common
findings.
• Up to two-thirds of patients have a reduced diffusing
capacity for carbon monoxide, and approximately onehalf have evidence of restrictive abnormalities on
pulmonary function tests . The predominant radiologic
abnormality in the chest is ground glass opacities
associated with septal thickening with a lower lobe
predominance . These findings are similar to those
seen in SSc-associated ILD.
• Treatment of ILD in mixed CTD is similar to
that of other CTD-ILDs. In one study, 47% of
patients with mixed CTD-ILD responded to
corticosteroids at a dose of 2 mg/kg/day for
6–8 weeks alone and rest of the patients with
CS in combination with CPH (2 mg/kg/day).
Ankylosing spondylitis
• It can affect the tracheobronchial tree and the lung parenchyma,
and respiratory complications include chest wall restriction, apical
fibrobullous disease with or without secondary pulmonary
superinfection, spontaneous pneumothorax, and obstructive
sleep apnea.
• Ankylosing spondylitis is a common cause of pulmonary apical
fibrocystic disease; early involvement may be unilateral or
asymmetrical, but most cases eventually consist of bilateral apical
fibrobullous lesions, many of which are progressive with
coalescence of the nodules, formation of cysts and cavities,
fibrosis, and bronchiectasis. Mycobacterial or fungal
superinfection of the upper lobe cysts and cavities occurs
commonly. Aspergillus fumigatus is the most common pathogen
isolated, followed by various species of mycobacteria.
• Prognosis of patients with fibrobullous apical
lesions is mainly determined by the presence,
extent, and severity of superinfection. Pulmonary
function test results are nonspecific and generally
parallel the severity of parenchymal involvement.
A restrictive ventilatory impairment can develop
in patients with ankylosing spondylitis because of
either fusion of the costovertebral joints and
ankylosis of the thoracic spine or anterior chest
wall involvement.
• Chest radiographic
findings may mirror the
severity of clinical
involvement.
Pulmonary
parenchymal disease is
typically progressive,
and cyst formation,
cavitation, and fibrosis
are seen in advanced
cases.
• No treatment has been shown to alter the
clinical course of apical fibrobullous disease.
Although several antiinflammatory agents,
such as infliximab, etanercept, and
adalimumab, are being used to treat
ankylosing spondylitis, their effects on
pulmonary manifestations are unclear.
Pulmonary manifestations of Behçet's disease
• Since Behçet's disease does not have
pathognomonic symptoms or laboratory findings,
the diagnosis is made on the basis of the criteria
proposed by the International Study Group for
Behçet's disease in 1990 . According to the
criteria, recurrent oral ulceration must be present
and at least two of the following: recurrent
genital ulceration, eye lesions, skin lesions, or a
positive pathergy test (development of a papule
or pustule following a needle prick to the skin ).
• Pulmonary artery aneurysms, arterial and
venous thrombosis, pulmonary infarction,
recurrent pneumonia, bronchiolitis obliterans
organised pneumonia, and pleurisy are the
main features of pulmonary involvement in
Behçet's disease.
• Pulmonary artery aneurysms affect mainly
young men. Haemoptysis of varying degrees
(up to 500 ml) is the most common and
predominant symptom. Rupture of an
aneurysm with erosion into a bronchus and the
development of in situ thrombosis from active
vasculitis have been suggested as explanations
for the haemoptysis.
• Sudden hilar enlargement or the appearance
of polylobular and round opacities on the chest
radiograph can represent pulmonary artery
aneurysms . When associated with an acute
episode of haemoptysis they appear poorly
marginated; otherwise, they have a distinct
outline
a thrombosed aneurysm of the
right pulmonary artery. The fuzzy
contour of the aneurysm wall and
perianeurysmal consolidation are
caused by an acute haemorrhage.
showing multiple aneurysms of
different branches of the
pulmonary arteries bilaterally.
• The treatment approach depends on the individual
patient, severity of disease, and major organ
involvement.
• Major vessel disease with thrombotic events are
treated with systemic anticoagulation in addition to
corticosteroids, azathioprine, cyclophosphamide, or
cyclosporine A.
• Pulmonary arterial aneurysms are treated with
cyclophosphamide and corticosteroids.
• Pulmonary aneurysms and areas that incur ischemic
damage due to vasculitis or thrombosis may require
resection.
Autoantibodies in Collagen-Vascular
Diseases
• Sometimes the classical systemic
manifestations of connective tissue disease
may not be well defined or sometimes
pulmonary presentation may be earlier than
the systemic manifestation. In those cases we
can performed the following tests as screening
purpose.
Autoantibody
RA
SLE
SD
SS
PM/DM
AS
MCTD
RF
+
+
+
+
rare
__
+
ANA
+
+
+
+
rare
__
+
Ds-DNA
__
+
__
__
__
__
__
Anticentromere
__
__
+ (limited)
rare
rare
__
__
Scl-70
__
__
+(diffuse)
rare
__
__
Anti-Jo
__
__
__
rare
+(ILD)
__
__
ANCA
rare
__
__
__
__
__
rare
Smith antibody
__
+
__
__
__
__
__
Anti-Ro/SSA and
anti-La/SSB
__
__
__
+
__
__
__
Anti-U1-RNP and
anti-UN-70 kd
__
__
__
__
__
__
+
__
__
__
__
__
__
Anti-CCP
+
Take home messages :
• Pulmonary evaluation is essential in all
rheumatological diseases.
• Pulmonary evaluation has become more
easier, with the interpretation of HRCT of
chest.
• If the patient present with DPLD, he/she
should under gone screening tests for the
rheumatological diseases.