Systemic disorders and the lung

By
Prof. Hatem El Mallawany
Professor and Head of Chest Department
Faculty of Medicine
Alexandria University
• The lung is a common site of
disease in several disorders which
primarily affect other organs.
• Such involvement can arise as part
of the underlying systemic
disorder, or as a complication of its
treatment.
 Respiratory manifestations of
systemic diseases and
conditions
• Rheumatic fever:
– It can lead to the following pulmonary
manifestations:
• Rheumatic pneumonia (treatment as
rheumatic activity).
• Pulmonary edema or pleural effusion
(from congestive heart failure).
• Pulmonary hemosiderosis.
• Pulmonary infarction.
• Rheumatoid disease:
– It can lead to the following pulmonary
manifestations:
• Pleural thickening and pleural effusion.
• Interstitial fibrosis.
• Rheumatoid nodule in coal worker (Caplan’s
syndrome).
• Lung nodules (single or multiple).
• Pleuroperocarditis.
• Pulmonary hypertension.
• Increased incidence of respiratory infections.
• Sjogren syndrome I.e. Sicca syndrome
which is a rheumatoid variant affecting
the lacrimal glands and salivary glands
(keratoconjunctivitis sicca).
• It causes decrease in the secretion of
the mucus glands of bronchi and thus
leads to dry cough, Secondar infection
and even pneumonia.
• Systemic Lupus Erythematosis (SLE):
– It can lead to the following pulmonary
manifestations:
• Pleural effusion, pleural thickening which may be
unilateral or bilateral (LE cells and antinuclear
factor are positive in the pleural aspirate).
• Interstitial fibrosis (IF).
• Pneumonic consolidation either directly due to
SLE or due to secondary infection.
• Pericarditis.
• Increased incidence of pulmonary embolism.
• Scleroderma (Progressive Systemic
Sclerosis):
– It can lead to the following pulmonary
manifestations:
• Interstitial fibrosis (IF).
• Dyspnea due to changes (fibrosis) in the chest
wall and diaphragm rather than the lungs.
• Aspiration (chemical) pneumonia from spill-over
from the dilated esophegus (which has decreased
peristalisis).
 • Pleural thickening or pleural effusion.
Scleroderma is one of the non-metastatic extra-
thoracic manifestations of bronchial carcinoma.
• Pulmonary edema secondary to heart failure from
systemic (renal) hypertension.
• Bronchiectasis.
– N.B: CREST syndrome is a type of
scleroderma in which there calcinosis of soft
tissues, Raynaud’s phenomena, esophageal
immobility, Sclerodactly i.e. changes and
ulcers in the fingers.
• Dermatomyositis
– It can lead to interstitial pulmonary
fibrosis, pneumonia and respiratory
muscle weakness which in turn can
cause hypoventilation.
• Stevens-Johnson syndrome
(erythema multiforme):
– Miliary or nodular shadows, areas of
consolidation or Mycoplasma (primary
atypical) pneumonia. It is provoked
by drugs as aspirin and
sulphonamides.
• Polyarteritis nodosa (PAN):
– It can lead bronchial asthma,
pulmonary eosinophilia and renal
hypertension (vasculitis). If a similar
condition is associated with
granuloma and ulceration in the
upper respiratory tract, it is described
as “Wegener’s granulmatosis).
– If a condition similar to PAN occurs
with marked eosinophilia, more
asthmatic attacks, increased blood
IgE level, extravascular granulomas
(not present in PAN), more systemic
manifestations and more lung
involvement, it is described as
“Churg-Strauss Syndrome” which is
allergic angiitis and granulomatosis.
• Pulmonary vasculitis:
– PAN, Wegener’s granulomatosis, Churg-
Strauss syndrome (necrotizing angiitis),
giant cell arteritis, rheumatoid arthritis,
scleroderma and sarcoidosis are
components of the group of diseases
described as “Pulmonary vasculitis”. Almost
every disease known to affect systemic
arteries may involve the pulmonary
circulation as well.
– This group also includes “Behcet’s disease”
characterized by orogenital mucocutaneous
ulcers. Fever, arthritis, erythema multiform
(Stevens-Johnson syndrome), vasculitis,
thrombophlebitis, and occlusion of blood
vessels such as retinal vessels (leading to
blindness), renal vessels (leading to uremia),
peripheral vessels (leading to deep vein
thrombosis and pulmonary embolization) or
superior vena cava (SVC) thus leading to
SVC obstruction syndrome.
 Sarcoidosis
• Sarcoidosis is a multi-system
granulomatous disorder of unknown
etiology which is characterized by
formation of non-caseating granuloma.
• It can affect almost every organ in the
body.
• Its variable clinical, immunological and
biochemical manifestations have been
intensively studied over the last
hundred years since the disorder was
first recognized.
• The most common presenting features
are bilateral hilar lymphadenopathy,
pulmonary infiltrations and skin or eye
lesions, but the spectrum of clinical
presentation is very wide and may
mimic other diseases.
• An acute onset with erythema nodosum
and bilateral hilar lymphadenopathy
heralds a benign self-limiting course
which can often be shortened by
corticosteroid therapy.
• An insidious onset is usually followed by
the development of progressive fibrosis
and organ damage. This may be
modified but not necessarily prevented,
by corticosteroid therapy.
• Granulomas are commonly distributed
throughout the body without causing
significant organ dysfunction but may
be concentrated in one or more organs
with striking clinical effects.
 Renal diseases
• Renal diseases can lead to the following
pulmonary manifestations:
– Pulmonary edema (cardiogenic or non-
cardiogenic i.e. ARDS). If this pulmonary
edema becomes repeated, it can lead to
hemosiderosis.
– Interstitial fabrosis.
– Pleural effusion or uremic pleurisy (dry
pleurisy)
– Pericarditis or pericardial effusion.
– Uremic pneumonitis or pneumonia and
recurrent infections.
– Metastatic pulmonary infarctions.
– Dialysis can lead to pleural effusion. This can
occur in peritoneal dialysis as well as in
hemodialysis.
– Hemodialysis can lead to air or pulmonary
embolism. Peritoneal dialysis can lead to
basal atelectasis (from elevation of the
diaphragm).
– In renal transplant, immunosuppressive
therapy is described to avoid rejection of the
transplanted kidney. This can predispose to
recurrent pulmonary infection.
– Pulmonary hemorrhage can occur in
Goodpasture’s syndrome in other
types of vasculitis.
– Perinephric or cortical abscess can
lead to staphylococcal pneumonia
through hematogenous spread of this
infection.
 Gastrointestinal diseases
• The following pulmonary manifestations
can be associated with gastrointestinal
diseases:
– Tracheo-esophageal fistula can cause
aspiration pneumonia or lung abscess.
– Gastrogenous cysts (gastroenteric or
enterogenous cysts) arising from the
esophagus appear as posterior mediastinal
lesion.
– Hiatal hernia appears as a posterior
mediastinal shadow with air-fluid
levels.
– Phayngo-esophageal diverticulum
(Zenker’s diverticulum) appears as a
superior mediastinal shadow an can
lead to recurrent aspiration
pneumonia.
Pulmonary manifestations of
gastrointestinal diseases
indirect associations
• Gastrointestinal • Pulmonary manifestations:
disorders: – Aspiration pneumonia, lung
– Pharyngeal pouch, abscess.
achalasia, gross reflux. – Abnormal chest radiograph.
– Achalasia, enterogenous
cyst, diaphragmatic
hernia, hiatus hernia,
pharyngeal pouch. – Esophageal-bronchial fistula
– Esophageal carcinoma. – Mediastinitis, pleural effusion.
– Esophageal rupture. – Pulmonary nodules,
– Carcinoma, lymphoma lymphangitis.
– Asthma, amyloid.

– Metastatic carcinoid
tumor.
Pulmonary manifestations of
intestinal disorders
• Intestinal disorders • Pulmonary
– Ulcerative colitis manifestations:
– Airways parenchyma
(localized large airway
stenoses, bronchiectasis,
chronic bronchitis,
fibrosing alveolitis,
organizing pneumonia).
– Crohn’s disease. – Airways diseases (as
above).
– Celiac disease – Extrinsic allergic
alveolitis, pulmonary
hemosiderosis,
tuberculosis, atopic
disease.
 Liver disorders
• Cirrhosis:
– Hepatic cirrhosis may be associated with cyanosis,
finger clubbing, and arterial oxygen desaturation
caused by multiple miscroscopic pulmonary
arteriovenous shuncts. Arteriovenous fistulas may
not be identified on a chest radiograph or in lung
biopsy specimens. Typically the gas transfer factor is
reduced, and the hypoxemia cannot be abolished by
giving patients 100% oxygen. Two-dimensional
echocardioghraphy with contrast may confirm the
diagnosis by demonstrating an intrapulmonary
shunt.
• Fibrosing alveolitis:
– Associations between fibrosing
alveolitis and primary biliary cirrhosis
and chronic active hepatitis have
been suggested.
 Pancreatic disorders
• Acute respiratory insufficiency:
– May occur in acute pancreatitis, and is
thought to be the major factor in 25% of
deaths from this condition. In survivors,
recovery appears to be complete with little
physiological evidence of lung damage.
• Pleural effusion:
– Occurs in up to 15% of patients with acute
pancreatitis and is typically on the left side
and painless (60%). Effusions are bilateral
in 30% of patients and on the right side in
10%.
 Endocrine disorders

• Obesity:
– An increased amount of fat in the
chest wall and abdomen reduces the
volume of the lungs and decreases
the compliance of the respiratory
system, particularly when the obese
patient lies flat. Hypoventilation
occurs, especially during rapid eye
movement sleep.
• Acromegaly:
– Enlargement of the soft tissues of the
nasopharynx may result in upper
airways obstruction and sleep-
disordered breathing with sleep
apnea, excessive nocturnal snoring
and daytime somnolence. This is one
of the major causes of premature
death in acromegaly.
• Thyroid disorders:
– Thyrotoxicosis patients often complain of
breathlessness. This is probably a result of
respiratory muscle weakness and increasing
metabolic rate. Dyspnea is also a common
complaint of hypothyroid patients, probably
caused by congestive cardiac failure,
anemia, pleural effusions, obesity, or any
combination of these.
• Diabetes mellitus:
– 60% of insulin-dependent diabetic patients
have pulmonary function abnormalities
(reduced gas-exchange and capillary blood
volume) due to pulmonary microangiopathy.
These changes are not usually evident
clinically. Pulmonary tuberculosis may be
reactivated in diabetes because cell-
mediated immunity is decreased.
 Neurological disorders
• Severe respiratory disorders can arise
indirectly from disordered ventilatory
control by te brain stem (e.g. Cheyen-
Stokes respiration) or from weakness of
the respiratory muscles. Respiratory
infections are the terminal event of
many neurological conditions,
particularly those with bulbar
involvement.
• Neurofibromatosis:
– Up to 33% of adult patients with
neurofibromatosis have interstitial
pulmonary pulmonary fibrosis.
 Hematological disorders

• Hematological disorders may be

associated with disorders of the
thoracic cage, mediastinum, lung,
pleura, or pulmonary vessels, this
may be a result of the underlying
disorder, drug therapy or infection.
• Lymphadenopathy:
– Up to 66% of patients with Hodgkin’s
disease may have enlarged
mediastinal lymph nodes, this is less
common in non-Hodgkin’s disease.
Typically, the lymph node
involvement is bilateral and
asymmetrical with both hilar and
mediastinal lymphadenopathy.
• Parenchymal involvement:
– Can occur in various hematological
disorders.
– Approximately 12% of patients with
Hodgkin’s disease have parenchymal
involvement at presentation, and 30-40%
have it at some stage in their illness. It is
almost invariably accompanied by
mediastinal lymph node enlargement.
• Pulmonary infiltrates on chest radiograph of a
patient with leukemia are more likely to be
caused by infection, cardiac failure, or
pulmonary hemorrhage than the leukemia.
Pulmonary nodules may occur in patients
whose leukemia relapses.

• Cytotoxic drugs have been linked to toxic

pulmonary parenchymal side-effects. The most
common clinical presentation is with
symptoms and signs suggestive of progressive
pulmonary fibrosis, with inspiratory crackles.
• Pleural involvement:
– Pleural effusions occur in
approximately 30% of patients with
Hodgkin’s and non-Hodgkin’s
lymphoma, usually in association with
intra-thoracic lymphadenopathy.
Effusions may also occur in cases of
leukemia as a consequence of the
disease or of infection.
Parasitic lung diseases
• Parasitic lung diseases may be
caused by:
– Protozoa: leading to:
• Amebic lung disease.
• Toxoplasmosis.
• Pneumocystis carinii pneumonia.
• Parasitic lung diseases may be
caused by:
– Helminths: e.g.:
• Cestodes (Hydatid cyst).
• Trematodes (Bronchoplulmonary
bilharziasis I.e. Schistosomiasis,
paragonimiasis).
• Nematodes e.g. ascaris, ancylostoma and
filaria.
 Thoracic amebiasis
• Entameba Histolytica penetrates the
intestinal veins to reach the liver where
it forms amebic liver abscess usually in
the right lobe of the liver. Inside the
abscess, there will be the classical
chocolate pus i.e. anchovy sauce pus.
• Such liver abscess may rupture into the
pleura or lung or into the pericardium or
the bowel.
 Thoracic amebiasis

• Fever, enlarged tender liver,

weight loss, pain in the lower chest
and shoulder may be found.
Leucocytosis, mild anemia and
raised sedimentation rate are also
present.
• Extension of infection through the
diaphragm may result in fibrinosis
pleurisy, pleural effusion or basal
pneumonia.
• Radiologically, there may be elevation
of the right hemi-diaphragm or
obliteration of the costo-phrenic angle
by pleural effusion.
 Pneumocystis Carinii
• This organism appears as minute oval
bodies or cysts 5-10 m in length and is
probably related to the protozoa. It
causes pneumonia in infants of a few
months of age and in adults who are
immunosuppressed.
• Breathlessness and tachypnea are the
main features, other physical signs are
rarely helpful.
 Pneumocystis Carinii
• Gas exchange becomes progressively
impaired with progressive fall in the
transfer factor and ultimately cyanosis.
• The X-ray shows widespread mottling
which is slowly progressive.
• The diagnosis may be confirmed by lung
biposy (usually transbronhial biopsy) or
broncho-alveolar lavage.
 Hydatid cyst
• The disease is caused by the cestode
Echinococcus granulosus. The definitive host in
the dog or wolf and the intermediate host is a
variety of mammals including man.
• The adult worm lives in the intestines of the
definitive host for 5-20 months. The terminal
segment detaches from the worm and releases
the ova with the stools. Ingestion of the ova
(on polluted vegetables, grass or water)
causes infection.
 Hydatid cyst

• Clinical picture:
– Clinical picture depends on whether
the cyst is intact or has ruptured.
 Hydatid cyst

• Clinical picture of the ruptured cyst:

– 30% of pulmonary cysts rupture,
especially those with a diameter greater
than 7 cm. Rupture may occur
spontaneously or as a result of coughing,
sneezing, muscular effort, trauma or as a
result of coughing, sneezing, muscular
effort, trauma to the chest or infection.
 Hydatid cyst
• Clinical picture of the ruptured cyst:
– A communication with the bronchial tree
allows air to leak into the potential space
between the pericyst and the laminar layer.
The air localizes at the superior aspect of
the cyst, giving rise to the meniscus
radiological sign (air cap or operculum) i.e.
halo appearance.
– Rupture of a cyst produces an abrupt cough
with expectoration and fever; hemoptysis is
common.
 Hydatid cyst
• Diagnosis:
– A high index of suspicion is invaluable, rural
residence and contact with dogs are
suggestive. Diagnosis is established
radiologically and serologically.
– The complement fixation test (Casoni test).
It is positive in 66% cases.
– The indirect hemagglutinin test. It is
positive in about 70% of cases.
 Hydatid cyst

• Treatment:
– Surgical excision is the best.
 Broncho-Pulmonary
Bilharziasis (Schistosomiasis)
• This includes:
– Verminous pneumonitis i.e. focal
pneumonia caused by the worms of
bilharziasis when reaching the lungs.
– Bilharzial granuloma or bilharzial
tubercles that represent a distinctive
reaction around the ovum after it
penetrates the vessel wall.
– Pleural effusion is reported secondary to
hypoproteinemia or after administration
of anti-bilharzial treatment.
– Demonstration of bilharzial ova in the
sputum was also reported.
– Bronchospasm simulating an asthamtic
attack can also occur early in the course
of the disease or during anti-bilharzial
treatment.
– Hemoptysis can occur during the larva
through the lung.
– Interstitial fibrosis can also occur.
– Transient pulmonary infiltration with
oesinophils.
– Bilharzial oval embolization usually
occur and is the usual cause of the
pulmonary disease. Impaction of the
ova in a pulmonary arteriole results in
an arteriolitis which destroys the
media of the vessel and provokes a
distinctive reaction round the ovum
after it penetrates the vessel wall
(bilharzial or schistosomal tubercle).
• The affected arteriole becomes occluded by
internal thickening (obliterative endarteriolitis).
New vessel formation and thus angiomatoid
formation may occur and becomes the site of
intra-pulmonary shunts.

• Pulmonary hypertension with aneurysmal

dilatation of the pulmonary arteries can occur as
a result of systolic overload on the right
ventricle and leads to development of bilharzial
cor pulmonale and increase in the size of cardiac
shadow in the chest X-ray.
• Diastolic overload of the right
ventricle can be an additional
factor in the pathogenesis of cor
pulmonale. Such diastolic overload
is secondary to the different types
of shunts which can occur in the
lungs of the bilharzial patients.
These include:
– Bronchial artery-pulmonary artery shunt:
This exposes the right ventricle to the high
pressure of the systemic circulation.
– Pulmonary artery-pulmonary vein
(precapillary) shunt: This can lead to
hypoxemia.
– Portal vein-pulmonary vein shunt: This type
can also cause hypoxemia in those patients.
– Porto-systemic shunts.
Pregnancy and the lung
Chest problems in pregnancy

• Asthma is the most common

pulmonary disease encountered
during pregnancy, occurring in
about 4-6% of pregnant women.
• Issues commonly raised by the
clinician caring for the pregnant
asthmatic include:
– How does pregnancy affect te natural
history of asthma.
– Effect of drugs in the child and the
chances of having an asthmatic child.
– Guidelines for the management of
asthma during pregnancy.
 To answer these questions

• A course of asthma during

pregnancy is impossible to predict,
but usually is no different to that
when the patient is not pregnant.
There is no good genetic reason for
an asthmatic to deny herself a
child.
• Drugs used in asthma are not known to
be toxic to the fetus.
• It is possible that very high doses of
steroids may have deleterious effect on
the early fetus. But it is likely that a
severe asthma attack could have also.
• Antibiotics will be discussed later.
• Antihistaminics should be carefully used
with pregnancy.
 Guidelines for treatment

• The same general principles of

therapy apply to pregnant
asthamtics.
• Early use of steroids in adequate
dose, might avoid the large doses
that might be required in the
hospital.
• But clearly it is wise to confine
treatment to inhaled drugs as far as
possible except during acute
exacerbations.
• Many inhalers could be used including
B2 agonists and the recent new B
adrenergic agents such as salmetrol and
formoterol, which are more selective for
B2 receptors and which have longer
duration of action.
• Also inhaled steroids are now
improved and the newer inhalers
have minimal blood absorption and
also longer duration of action.
• Lastly assurance is a very
important drug.
What about TB in pregnancy?

• Women with symptoms suggestive

of pulmonary TB should have an
appropriately shielded chest x-ray
performed regardless of the stage
of pregnancy.
• Therapy:
– The benefits of treating active TB in
pregnancy outweigh any potential
drug toxicity. Pregnancy does not
affect the response to antituberculous
drugs, and TB is not a medical
indication for abortion.
– Streptomycin is not used because of
possible ototoxicity to the fetus.
• Pyrazinamide is not recommended
because of lack of data on the risk for
teratogenicity.

• The accepted regimen for therapy

includes Rifampicin, isoniazid and
ethambutol in the initial two-month
phase, followed by seven months of
Rifampicin and isoniazid.
Management of venous
Thromboembolism and
pulmonary embolism in
pregnancy
• First: In achieving a diagnosis,
isotope lung scan and radioactive
fibrinogen uptake studies cannot
be used in pregnancy
(Conventional chest X-ray and
ascending venography are
permissible with pelvic shielding).
• Secondly: Coumarin compounds
(Warfarin) cross the placental
barrier and are not given in the
first trimester and if possible
during the whole pregnancy
especially after the 36th week.
• Heparin does not cross the placenta and
is not teratogenic, given IV or SC.

• Other forms as low dose unfractionated

heparin or low molecular weight heparin
are practical. The new antithrombotics
such as Hirudin and Hirulog are direct
thrombin inhibitors and are very
effective.