2. SARCOIDOSIS
Definition :Sarcoidosis is a multisystem
disorder of unknown etiology
characterized by non caseating granuloma
which affects mainly lung but can also any
other organs .
3. EPIDEMIOLOGY
It occurs mainly in 3rd or 4th decade of life
More predominant in women with an
incidence of 6.3 vs 5.9 cases per 100,000
person-years.
Lifetime risk for US whites is 0.85 percent
compared with 2.4 percent in US blacks.
More prevalent in Swedes, Danes, and US
blacks.
4. EPIDEMIOLOGY
Annual incidence in the U.S. is 10/100,000
among whites and 36/100,000 among African
Americans.
Most commonly seen in the mid-Atlantic and
Southern Atlantic states but rare in the
Southwest.
Affects siblings of first- or second- degree
relatives in 15% of patients with sarcoidosis.
Familial cases described in 17% of African
Americans, but only 6% of whites.
5. ETIOLOGY AND PATHOGENESIS
Etiology of sarcoidosis is remain unknown, but
several lines of evidence suggest that it is a
disease of disordered immune regulation in
genetically predispose individual.
Immunological Factor
There are several immunological abnormalities
in the granuloma of sarcoidosis that suggest
the development of cell mediated response to
an unidentified antigen. These process are
driven by CD4+T Cell.
6. ETIOLOGY AND PATHOGENESIS
Intra-alveolar and interstitial accumulation of
CD4+T cell ,resulting CD4/CD8 T cell ratio
ranging from 5:1 to 15:1.There is oligoclonal
expansion of T-cell subsets as determined by
analysis of T cell receptor rearrangement,
suggesting an antigen driven proliferation.
Increase levels of T-cell derived TH 1
cytokines such as IL-2 and IFN-у resulting in
T-cell expansion and macrophage activation
respectively.
7. ETIOLOGY AND PATHOGENESIS
Increase levels of cytokines in the local
envirment (IL-8,Macrophage
inflammatory protein 1 α ) that favour
recruitment of additional T cell and
Macrophage and contribution to the
formation of granulomas. TNF in
particular release of high levels by
activated alveolar macrophage and the
TNF concentration in the broncho
alveolar fluid is a disease activity.
14. ETIOLOGY AND PATHOGENESIS
Genetic Factor
Evidence of genetic influences are the
familial and racial clustering of cases
and the association with certain HLA
genotypes
(eg:HLA-A1and HLA-B8)
15. ETIOLOGY AND PATHOGENESIS
Envirment factor
These are possibly the most tenuous of all
the associations in the pathogenesis of
sarcoidosis. As with many other diseases
of unknown etiology, suspicion fall on
microbes. Indeed several putative
microbes have been proposed as the
inciting agent for sarcoidosis (eg-
mycobacteria, propionobacterium acnes,
Rickettsia species)
16. MORPHOLOGY
Histologically all involved tissues show the
classic well formed noncaseating
granuloma, each composed of an
aggregates of tightly clustered epithelioid
cell, often with langhans or foreign body
giant cell, central necrosis is unusual with
chronicity the granulomas may become
enclosed within fibrous rimes or may be
eventually be replaced by hyaline fibrous
scars.
17. MORPHOLOGY
laminated concentration composed of
calcium and proteins known as
schaumann bodies and stellate inclusion
as asteroid bodies enclosed with in giant
cells are formed in approximately 60% of
granulomas.though characteristic these
microscopic features are not pathognomic
of sarcoidosis because asteroid and
schaumann bodies may be encounteered
in other granulomatous disease
27. PULMONARY SARCOIDOSIS
First side of involvement
Begain with alveolitis involving small
bronchi and small blood vessels
Alvveolitis either clear up spontaneously
or lead to granuloma or fibrosis
28. PULMONARY SARCOIDOSIS
Microscopically. There is usually no
demonstrable alteration , although in
advanced cases the coalescence of
granuloma produce small nodule that are
palpable or visible as 1 to 2cm
noncaseating, noncavitary consolidation.
29. PULMONARY SARCOIDOSIS
Histologically. The lesion are distributed
primarily along the lymphatic's, around the
bronchi and blood vessels, although
alveolar lesion are also seen in relative
frequency. The granulomas in the
bronchial sub mucosa account for the high
diagnostic yield of bronchoscopic biopsy.
There seems to be a strong tendency for
lesion to heals in the lungs, so varying
stages of fibrosis, hyalinization are not
found
49. NODULAR PATTERN
SMALL 5MM NODULES ARE SUBPLEURAL, ALONG FISSURES AND
BRONCHOVASCULAR BUNDLES. GIVE THE VESSELS (ARROW) AND
FISSURES A BEADED APPEARANCE.
50. LYMPH NODES WITH RIM (EGGSHELL) CALCIFICATION (ARROW)
ARE RARE IN SARCOIDOSIS BUT COMMON IN SILICOSIS.
55. CLINICAL PRESENTATION
Most patients have the pulmonary
manifestations, most commonly
presenting with incidental findings on
CXR.
Interstitial disease
Symptoms include dry cough, dyspnea,
and chest discomfort
Unpredictable course
56. PROGNOSIS OF PULMONARY
SARCOIDOSIS
Prognosis of
pulmonary sarcoidosis
3/4 1/3 1/5
Complete resolution
of
hilar
lymphadenopathy
Complete resolution
of
parenchymal
disease
Irreversible
pulmonary
fibrosis
58. SARCOIDOSIS OF LYMPH NODES
Lymphadnopathy
Lymph nodes are involved in almost all
cases particularly the hilar and medistinal
nodes, but any other nodes may be
involved .nodes are characteristically
enlarge discrete and sometimes calcified
Tonsil may affected in about quarter to
one third of the cases
59. LYMPHADENOPATHY
Typical
1.Bilateral hilar & right paratracheal LN,
2.Middle mediastinal LN occur in 50% of cases.
3.Left paratracheal, aorto-pulmonary &
subcarinal LN.
1-2-3 sign present in 95% of cases. This is
called Garland triad
76. 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
90. 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
91. SPLEEN & LIVER GRANULOMAS
THE SMALL LOW ATTENUATION LESIONS IN THE LIVER AND
SPLEEN IN SARCOIDOSIS.
94. 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
95. PUNCHED OUT LYTIC LESIONS
FOCAL OSTEOLYTIC LESIONS IN THE FINGERS ARE MOST
COMMON ABNORMALITY.
100. 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
101. T1-W POST GADOLINIUM MR IMAGE
POST CONTRAST IMAGE OF HIGH SIGNAL INTENSITY
TEMPORAL LOBE SARCOID LESION (ARROW)
102. T2-W MR IMAGE
HIGH SIGNAL INTENSITY EDEMA SURROUNDING BIOPSY
PROVEN SARCOID LESION.
105. 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
107. KIDNEY
Increased calcium absorption in
the gut
Related to high levels of circulating
1,25-dihydroxy vitamin D produced
by mononuclear phagocytes in
granulomas
114. 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%
115. 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
116. ADENOPATHY AT TIME OF DIAGNOSIS
MARKED ENLARGED HILAR AND MEDIASTINAL LYMPH
NODES.
117. ADENOPATHY DECREASED 2 YRS LATER
LYMPH NODES ARE SMALLER AND THERE IS PARENCHYMAL
LUNG DISEASE.
118. 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.
119. THE KVEIM-SILTZBACH TEST
The Kveim-Siltzbach skin test is based upon studies conducted
by Dr. Morten Ansgar Kveim, a Norwegian dermatologist, and
published in 1941. The test was later studied extensively and
popularized by Dr. Louis Siltzbach at the Mt. Sinai Medical
Center in New York City. It is the only test that, if positive, is
considered to be diagnostic of sarcoidosis. The test material,
a suspension of granuloma-containing spleen, lymph node, or
other tissue from a confirmed case of sarcoidosis, is injected
intradermally. A positive test is characterized by the formation
of a papule at the site of injection within 4-6 weeks which, on
microscopic examination, exhibits non-necrotizing
granulomas and the absence of foreign material.
120. THE KVEIM-SILTZBACH TEST
The Kveim test has been reported to be positive in a mean of
78% of patients with sarcoidosis worldwide (range 54%-
92%). A satisfactory test suspension will identify at least
60% of patients with active sarcoidosis and will yield no
more than 1% of false positive results in individuals without
sarcoidosis. A positive Kveim test assures a diagnosis of
sarcoidosis in 97%-98% of responsive individuals. The test
material must be validated by comparison with a previously
validated suspension in patients with and without
sarcoidosis.
121. THE KVEIM-SILTZBACH TEST
Because of the difficulties involved in preparation,
standardization and validation of the test material
as well as significant variation in the sensitivity
and specificity of test suspensions obtained from
different sources, the need for a biopsy procedure
and the wait of 4-6 weeks for a diagnosis, the
Kveim test has been largely replaced by
transbronchial biopsy for the diagnosis of
sarcoidosis. At the present time validated Kveim
test suspensions are available for diagnostic use
at very few institutions worldwide.
122. KVEIM TEST - SKIN BIOPSY
NON-NECROTIZING GRANULOMAS
123. KVEIM TEST - SKIN BIOPSY
NON-NECROTIZING GRANULOMAS
124. KVEIM TEST - SKIN BIOPSY
NON-NECROTIZING GRANULOMAS
Asteroid bodies are stellate inclusions with numerous rays radiating from a central core that are present in the cytoplasm of giant cells. . They may be be seen in sarcoidosis and other granulomatous disorders. They are most frequently encountered in the giant cells of foreign body granulomas
