Transcript Sarcoidosis

Sarcoidosis
Copyright Thorax.us 2005 Ramesh Kaul,MD
What is Sarcoidosis?
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Chronic multi system disorder
Unknown cause
Most affected organ is the lung
Skin, eyes and lymph nodes are
frequently involved
• Acute or sub acute and self
limiting
• Waxing and waning over years
Etiology
Results from exaggerated cellular
immune response (acquired,
inherited or both) to a limited class
of antigens or self antigens.
Etiology
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A defect in the immune system
An unidentified toxic substance
An unknown environmental cause
An inherited or genetic cause
A viral or bacterial infection
Incidence and Prevalence
• In all races and both sexes
• Risk greatest in a young black
woman
• Scandinavian, German, Irish, or
Puerto Rican origin
• 5/100,000 whites in the US have
sarcoidosis
• 40/100,000 blacks
Incidence and Prevalence
• 20 cases/100,000 in cities on the
east coast
• 20 to 40 years of age
• Black women gets sarcoidosis
twice black men
• White women equal white men
Pathophysiology
• Accumulation of mononuclear
inflammatory cells and T helper
lymphocytes
• Formation of granulomas,
aggregates of macrophages,
epithelioid cells and
multinucleated giant cells
LANGHANS' GIANT CELL
Langhans' giant cell in center of granuloma is
surrounded by epithelioid cells .
ADVANCED COLLAGENOUS FIBROSIS
Elongated fibroblasts (FB) with extensive
collagenous tissue (C). Giant cells (arrows)
Pathophysiology
• Giant cells in the central part of the
granuloma
• The central epithelioid and giant
cells are surrounded by a rim of
lymphocytes, mostly T-helper cells
• T-cell lymphocytes are increased in
areas of active granulomas
CYTOPLASMIC INCLUSION BODY
Schaumann body (arrow) is common in sarcoidosis
but is nonspecific.
Pathophysiology
• T-helper cells to T-suppressor cells
ratio is increased
• Exaggerated T-cell activity
indicates an altered immune
response
• Hyper globulinemia
• Mass affect of granulomas
damages the tissues
Clinical Manifestations
• 50% patients are asymptomatic
• Abnormal "routine" chest
radiograph
• Symptomatic patients, with wide
variety of symptoms
• Onset is usually insidious but can
be acute
Clinical Manifestations
• Respiratory symptoms are most
common
• Cough, chest discomfort, and
dyspnea
• Symptoms reflect the specific
organs involved by the granulomas
Lungs
• First site involved
• Begins with alveolitis involving
small bronchi and small blood
vessels
• Alveolitis either clears up
spontaneously or leads to
granuloma
• Fibrosis
Noncaseating granuloma in lung is the
characteristic lesion of sarcoidosis.
CASEOUS NECROSIS
Cellular destruction in TB granuloma appears as clumped
debris (arrows). This necrosis does not occur in sarcoidosis.
M. tuberculosis BACILLI
Caseous necrosis is most common in TB, but Gram negative,
acid fast bacilli must be identified to make the diagnosis.
SUBPLEURAL GRANULOMA IN LUNG
Eyes
• 25% have eye lesions
• Blurred vision, pain, photophobia
and dry eyes
• Chronic uveitis leads to glaucoma,
cataracts and blindness
• Keratoconjunctivitis sicca
• Papilledema
CONJUNCTIVITIS
PAPILLEDEMA
Often associated with 7th nerve facial palsy.
Skin
• 33% have skin lesions
• Cutaneous anergy is common.
• LOFGREN'S SYNDROME; acute
triad of erythema nodosum, joint
pains, and bilateral hilar adenopathy
NAKED GRANULOMA
Young granulomas (arrows) in the skin with no
surrounding rim of mononuclear cells.
ERYTHEMA NODOSUM
These reddish raised lesions.
Skin
• Lupus pernio- indurated blue
purple swollen shiny lesions on
nose, cheeks, lips, ears and
fingers.
• Papules, nodules, and plaques
• Psoriatic like lesions
• Lesions in scars and tattoos
LUPUS PERNIO
Facial lesions are most common, but the extremities
and buttocks can be involved.
LUPUS PERNIO
Indurated and violaceous range from a few
small lesions to large lesions
SMALL NODULES
Papules and nodular lesions, can be found anywhere on the body.
Papules are often multiple while nodules are often solitary.
RAISED PLAQUES
These raised plaques are the result of coalescence
of nodules.
PSORIASIS LIKE LESIONS
These small white lesions closely resemble
psoriasis.
Liver
• 33% have hepatomegaly or
biochemical evidence of disease
• Symptoms usually absent
• Cholestasis, fibrosis, cirrhosis, portal
hypertension, and the Budd-Chiari
syndrome have been seen
SPLEEN & LIVER GRANULOMAS
The small low attenuation lesions in the liver and
spleen in sarcoidosis.
EARLY COLLAGEN FORMATION
Extracellular collagen (C) is being produced by
fibroblasts
Musculoskeletal
• Acute polyarthritis with fever is
common
• Arthritis is self limited
• Chronic destructive bone disease
with deformity is rare
• Polymyositis and chronic myopathy
• Muscle disease is rare
PUNCHED OUT LYTIC LESIONS
Focal osteolytic lesions in the fingers are most
common abnormality.
LACY TRABECULAR PATTERN
Osteolysis has left a lacy trabecular pattern in this
phalanx (arrow)
DEFORMING LESIONS
Advanced sarcoidosis with osteolytic lesions of the
distal forearm, wrist, and bones of the hand
SCLEROTIC LESION
Rare and often in the axial skeleton.
SCLEROTIC LESIONS,
NONSPECIFIC
Focal sclerosis (arrows) of distal phalanges is unusual
NASAL BONE LESION
Nasal sarcoidosis can lead to osteolysis of the nasal
bone (arrows).
Heart
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5% have heart involvement
Conduction abnormalities
Cardiomyopathy
Chest pain
Intractable arrythmias
Sudden death
Nervous System
• Cranial nerves, and peripheral nerves
can be involved
• 7th nerve facial palsy is most
common
• Acute, transient, and can be
unilateral or bilateral
• HEREFORDT'S SYNDROME; facial
palsy accompanied by fever, uveitis,
and enlargement of the parotid gland
T1-W POST GADOLINIUM MR IMAGE
Post contrast image of high signal intensity
temporal lobe sarcoid lesion (arrow)
T2-W MR IMAGE
High signal intensity edema surrounding biopsy
proven sarcoid lesion.
Nervous System
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Optic nerve dysfunction
Papilledema
Palate dysfunction
Hearing abnormalities
Paresthesias
Meningeal granulomas
Encephalopathy
Kidney
• Granulomatous interstitial nephritis
produces renal failure
• Develops over a period of weeks to
months
• Rapid response to steroid therapy
• Kidney stones (nephrolithiasis) and
nephrocalcinosis are very unusual
secondary to hypercalcemia and
hypercalciuria
NEPHROCALCINOSIS
There are multiple calcifications of the kidneys.
Enlarged retroperitoneal lymph nodes (arrows)
Kidney
• Increased calcium absorption in
the gut
• Related to high levels of circulating
1,25-dihydroxy vitamin D produced
by mononuclear phagocytes in
granulomas
Lymph Nodes
• Lymphadenopathy
• Intrathoracic nodes enlarged in 7590% patients including hilar nodes
and paratracheal nodes.
• Peripheral lymphadenopathy
Enlarged bilateral hilar, right paratracheal
(arrow), and aortopulmonary window (arrowhead)
nodes.
CALCIFIED LYMPH NODES
late manifestation in 5% of patients.
PARACARDIAC LYMPH NODE
ABDOMINAL LYMPHADENOPATHY
Multiple enlarged paraaortic, paracaval, and porta
hepatis lymph nodes (arrows).
GASTRIC SARCOID
Granuloma involves the gastric antrum leading to
irregular nonspecific narrowing.
COLONIC SARCOID
Irregular narrowing of the rectosigmoid has the
appearance of inflammatory disease or malignancy.
Lab Abnormalities
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Lymphocytopenia
Mild eosinphilia
Increased E.S.R
Hyperglobulenemia
Lab Abnormalities
• Elevated level of angiotensin
converting enzyme
• Gallium 67 lung scan showing a
pattern of diffused uptake.
• Bronchiole alveolar lavage shows
increased lymphocytes
Radiography
•CXR 3 classic patterns are seen.
Type 1- bilateral hilar adenopathy with no
parenchymal abnormalities.
Type 2- bilateral hilar adenopathy with
diffused parenchymal changes.
Type 3- diffused parenchymal changes
without hilar adenopathy.
STAGE I
Thoracic lymphadenopathy. Normal lung
parenchyma. (50%)
STAGE II
Hilar and mediastinal lymphadenopathy. Abnormal
lung parenchyma. ( 30% )
STAGE III
Abnormal lung parenchyma. No lymphadenopathy. (
15% )
STAGE IV
Extensive pulmonary fibrosis is typically worst in
the upper lobes.
STAGE IV
Broad bands of fibrosis in the upper lobes.
MILIARY SARCOIDOSIS
CT shows well defined lung nodules less than 5mm
in diameter. This pattern is rare.
ALVEOLAR SARCOIDOSIS
Multiple lung masses are an unusual form of
sarcoidosis, resembles lung metastases.
ALVEOLAR SARCOIDOSIS
Computed tomography shows a mass which has air
containing bronchi (arrows) within it.
CAVITARY SARCOIDOSIS
Rare pattern of multiple cavitary sarcoid lung
lesions. Note lymphadenopathy.
RETICULONODULAR PATTERN
Common appearance of sarcoidosis involving the
lung parenchyma.
RETICULONODULAR PATTERN CLOSEUP
Well defined linear and nodular densities
characteristic of lung interstitial disease.
ACINAR PATTERN
Poorly defined nodular opacities are the size of
pulmonary acini (6mm).
PNEUMONIC APPEARANCE
Confluent acinar opacities look similar to
pneumonic consolidation.
NODULAR PATTERN
Small 5mm nodules are subpleural, along fissures and
bronchovascular bundles. Give the vessels (arrow) and fissures a
beaded appearance.
Lung Function Test
• Lung function abnormalities for
interstitial lung disease with
decreased lung volumes and
diffusing capacities
Radiography
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“Egg shell” calcification of hilar nodes
Plural effusions
Cavitations
Atelectasis
Pulmonary hypertension
Pneumothorax
Cardiomegaly
Lymph nodes with rim (eggshell) calcification
(arrow) are rare in sarcoidosis but common in
silicosis.
SUBPLEURAL NODULES
Cluster of small nodules looks like a tumor on a
radiograph.
MOST COMMON PATTERN
Bilateral symmetric hilar and right paratracheal
mediastinal adenopathy.
LYMPHADENOPATHY ON CT
Para-aortic and retrocaval lymphadenopathy. CT shows
enlarged lymph nodes not visible on radiographs.
POSTERIOR MEDIASTINAL LYMPH NODE
next to the aorta (A). Bilateral hilar adenopathy was
also shown.
STAGE IV
Permanent lung fibrosis. (20%)
Diagnosis
• Difficult to differentiate from chronic
infections, fungal diseases, T.B. and
lymphoma.
• Based on combined clinical,
radiologic and histologic findings.
• Laboratory tests seldom important
• Asymptomatic
Diagnosis
• Identify noncaseating granulomas
• Variety of infections
• Transbronchial biopsies positive in
65-95%, even if no lung parenchymal
abnormalities imaged.
• Tissue from mediastinoscopy
positive in 95%
• Scalene node biopsy positive in 80%
ADENOPATHY AT TIME OF DIAGNOSIS
Marked enlarged hilar and mediastinal lymph nodes.
ADENOPATHY DECREASED 2 YRS LATER
Lymph nodes are smaller and there is parenchymal
lung disease.
Diagnosis
• KVEIM TEST
• Involves injecting standardized
preparation of sarcoid tissue
material into the skin.
• Unique lump formed at the point of
injection is considered positive for
sarcoidosis.
Diagnosis
• Test not always positive
• Not used often in US
• Test material not approved for
sale by FDA.
Prognosis
• Good
• 50% have some permanent
organ dysfunction
• In 15-20% remains active or
recurs intermittently.
Treatment
• No known cure
• Corticosteroids, primary treatment
for inflammation and granuloma
formation.
• Prednisone, 1 mg/kg for 4-6 weeks
followed by slow taper over 2-3
months.
Treatment
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Chloroquine
Effectiveness ?
D-penicillamine.
Effectiveness ?
Chlorambucil
Azathioprine
Methotrexate might suppress alveolitis
Cyclophosphamide may suppress alveolitis
Treatment
• Risk of drugs high, in pregnant
women.
• Cyclosporine, evaluated in one
controlled trial was found
unsuccessful.