1. Copyright Thorax.us 2005 Ramesh Kaul,MD
Sarcoidosis
Ramesh Kaul, MD,MS,FCCP
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What is Sarcoidosis?
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
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Etiology
Results from exaggerated cellular immune response (acquired, inherited or both) to a limited class of antigens or self antigens.
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Etiology
A defect in the immune system
An unidentified toxic substance
An unknown environmental cause
An inherited or genetic cause
A viral or bacterial infection
(Sarcoidosis is not contagious, but resembles tuberculosis)
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5. 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
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6. 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
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Pathophysiology
Accumulation of mononuclear inflammatory cells and T helper lymphocytes
Formation of granulomas, aggregates of macrophages, epithelioid cells and multinucleated giant cells
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LANGHANS' GIANT CELL Langhans' giant cell in center of granuloma is surrounded by epithelioid cells .
Note peripherally arranged nuclei in giant cell.
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ADVANCED COLLAGENOUS FIBROSIS Elongated fibroblasts (FB) with extensive collagenous tissue (C). Giant cells (arrows)
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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
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CYTOPLASMIC INCLUSION BODY Schaumann body (arrow) is common in sarcoidosis but is nonspecific.
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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
Mediators do not cause the massive damage. It is the granulomas. Not chemical but anatomical cause.
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13. 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
sarcoidosis can involve one or more body systems and present wide variety of signs and symptoms which can be constitutional; fatigue, weight loss, fever and malaise generalized; or focused on a single organ
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14. Clinical Manifestations
Respiratory symptoms are most common
Cough, chest discomfort, and dyspnea
Symptoms reflect the specific organs involved by the granulomas
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Lungs
First site involved
Begins with alveolitis involving small bronchi and small blood vessels
Alveolitis either clears up spontaneously or leads to granuloma
Fibrosis
Fibrosis can form, causing the lung to stiffen and making breathing even more difficult.
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Noncaseating granuloma in lung is the characteristic lesion of sarcoidosis.
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CASEOUS NECROSIS Cellular destruction in TB granuloma appears as clumped debris (arrows). This necrosis does not occur in sarcoidosis.
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M. tuberculosis BACILLI Caseous necrosis is most common in TB, but Gram negative, acid fast bacilli must be identified to make the diagnosis.
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19. SUBPLEURAL GRANULOMA IN LUNG
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Eyes
25% have eye lesions
Blurred vision, pain, photophobia and dry eyes
Chronic uveitis leads to glaucoma, cataracts and blindness
Keratoconjunctivitis sicca
Papilledema
Acute uveitis (anterior or posterior) presents with discomfort, photophobia, blurred vision, and a red eye.
When the parotid gland is involved the mouth is dry also.
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CONJUNCTIVITIS
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22. PAPILLEDEMA Often associated with 7th nerve facial palsy.
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Skin
33% have skin lesions
Cutaneous anergy is common.
LOFGREN'S SYNDROME; acute triad of erythema nodosum, joint pains, and bilateral hilar adenopathy
These lesions can be the presenting finding of the disease.
LOFGREN'S SYNDROME, is highly suggestive of sarcoidosis.
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NAKED GRANULOMA Young granulomas (arrows) in the skin with no surrounding rim of mononuclear cells.
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25. ERYTHEMA NODOSUM These reddish raised lesions.
Lesions resolve spontaneously in weeks.
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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
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LUPUS PERNIO Facial lesions are most common, but the extremities and buttocks can be involved.
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LUPUS PERNIO Indurated and violaceous range from a few small lesions to large lesions
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SMALL NODULES Papules and nodular lesions, can be found anywhere on the body. Papules are often multiple while nodules are often solitary.
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RAISED PLAQUES These raised plaques are the result of coalescence of nodules.
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PSORIASIS LIKE LESIONS These small white lesions closely resemble psoriasis.
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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
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SPLEEN & LIVER GRANULOMAS The small low attenuation lesions in the liver and spleen in sarcoidosis.
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EARLY COLLAGEN FORMATION Extracellular collagen (C) is being produced by fibroblasts
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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
The arthritis ranges from mild with no physical findings to severe with swelling and tenderness.
Arthritis is self limited and usually lasts for weeks to months.
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PUNCHED OUT LYTIC LESIONS Focal osteolytic lesions in the fingers are most common abnormality.
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LACY TRABECULAR PATTERN Osteolysis has left a lacy trabecular pattern in this phalanx (arrow)
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DEFORMING LESIONS Advanced sarcoidosis with osteolytic lesions of the distal forearm, wrist, and bones of the hand
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39. SCLEROTIC LESION Rare and often in the axial skeleton.
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SCLEROTIC LESIONS, NONSPECIFIC Focal sclerosis (arrows) of distal phalanges is unusual
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NASAL BONE LESION Nasal sarcoidosis can lead to osteolysis of the nasal bone (arrows).
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Heart
5% have heart involvement
Conduction abnormalities
Cardiomyopathy
Chest pain
Intractable arrythmias
Sudden death
Heart dysfunction is most often due arrythmias, conduction abnormalities, or cardiomyopathy. There may be chest pain, intractable arrythmias, or heart failure without an evident etiology.
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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
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T1-W POST GADOLINIUM MR IMAGE Post contrast image of high signal intensity temporal lobe sarcoid lesion (arrow)
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T2-W MR IMAGE High signal intensity edema surrounding biopsy proven sarcoid lesion.
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Nervous System
Optic nerve dysfunction
Papilledema
Palate dysfunction
Hearing abnormalities
Paresthesias
Meningeal granulomas
Encephalopathy
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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
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NEPHROCALCINOSIS There are multiple calcifications of the kidneys. Enlarged retroperitoneal lymph nodes (arrows)
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Kidney
Increased calcium absorption in the gut
Related to high levels of circulating 1,25-dihydroxy vitamin D produced by mononuclear phagocytes in granulomas
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Lymph Nodes
Lymphadenopathy
Intrathoracic nodes enlarged in 75-90% patients including hilar nodes and paratracheal nodes.
Peripheral lymphadenopathy
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Enlarged bilateral hilar, right paratracheal (arrow), and aortopulmonary window (arrowhead) nodes.
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52. CALCIFIED LYMPH NODES late manifestation in 5% of patients.
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53. PARACARDIAC LYMPH NODE
There is an enlarged right paracardiac lymph node (arrows). CT shows more lymph nodes than radiographs and more accurately locates the nodes. This is important in deciding which procedure should be used; mediastinoscopy, bronchoscopy, Chamberlin procedure, or percutaneous biopsy, if it is necessary to biopsy a node
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ABDOMINAL LYMPHADENOPATHY Multiple enlarged paraaortic, paracaval, and porta hepatis lymph nodes (arrows).
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GASTRIC SARCOID Granuloma involves the gastric antrum leading to irregular nonspecific narrowing.
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COLONIC SARCOID Irregular narrowing of the rectosigmoid has the appearance of inflammatory disease or malignancy.
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Lab Abnormalities
Lymphocytopenia
Mild eosinphilia
Increased E.S.R
Hyperglobulenemia
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Lab Abnormalities
Elevated level of angiotensin converting enzyme
Gallium 67 lung scan showing a pattern of diffused uptake.
Bronchiole alveolar lavage shows increased lymphocytes
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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.
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60. STAGE I Thoracic lymphadenopathy. Normal lung parenchyma. (50%)
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STAGE II Hilar and mediastinal lymphadenopathy. Abnormal lung parenchyma. ( 30% )
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62. STAGE III Abnormal lung parenchyma. No lymphadenopathy. ( 15% )
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STAGE IV Extensive pulmonary fibrosis is typically worst in the upper lobes.
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64. STAGE IV Broad bands of fibrosis in the upper lobes.
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MILIARY SARCOIDOSIS CT shows well defined lung nodules less than 5mm in diameter. This pattern is rare.
These lung lesions are indistinguisable from miliary tuberculosis, fungal disease and a variety of other diseases.
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ALVEOLAR SARCOIDOSIS Multiple lung masses are an unusual form of sarcoidosis, resembles lung metastases.
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ALVEOLAR SARCOIDOSIS Computed tomography shows a mass which has air containing bronchi (arrows) within it.
In addition to sarcoidosis, bronchioloalveolar carcinoma, lymphoma, and pseudolymphoma can present as a mass with air bronchograms.
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CAVITARY SARCOIDOSIS Rare pattern of multiple cavitary sarcoid lung lesions. Note lymphadenopathy.
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RETICULONODULAR PATTERN Common appearance of sarcoidosis involving the lung parenchyma.
Note enlarged hilar lymph nodes.
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RETICULONODULAR PATTERN CLOSEUP Well defined linear and nodular densities characteristic of lung interstitial disease.
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ACINAR PATTERN Poorly defined nodular opacities are the size of pulmonary acini (6mm).
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PNEUMONIC APPEARANCE Confluent acinar opacities look similar to pneumonic consolidation.
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NODULAR PATTERN Small 5mm nodules are subpleural, along fissures and bronchovascular bundles. Give the vessels (arrow) and fissures a beaded appearance.
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Lung Function Test
Lung function abnormalities for interstitial lung disease with decreased lung volumes and diffusing capacities
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Radiography
“Egg shell” calcification of hilar nodes
Plural effusions
Cavitations
Atelectasis
Pulmonary hypertension
Pneumothorax
Cardiomegaly
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Lymph nodes with rim (eggshell) calcification (arrow) are rare in sarcoidosis but common in silicosis.
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SUBPLEURAL NODULES Cluster of small nodules looks like a tumor on a radiograph.
Note nodular thickening of the major fissure which is a typical distribution of sarcoid nodules.
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MOST COMMON PATTERN Bilateral symmetric hilar and right paratracheal mediastinal adenopathy.
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LYMPHADENOPATHY ON CT Para-aortic and retrocaval lymphadenopathy. CT shows enlarged lymph nodes not visible on radiographs.
CT demostrates enlarged lymph nodes which are not visible on radiographs.
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POSTERIOR MEDIASTINAL LYMPH NODE next to the aorta (A). Bilateral hilar adenopathy was also shown.
The posterior mediastinum is the least common site of adenopathy in sarcoidosis, but transbronchial biopsy showed nonceaseating granulomas. The nurse remains asymptomatic ten years later.
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81. STAGE IV Permanent lung fibrosis. (20%)
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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
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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%
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ADENOPATHY AT TIME OF DIAGNOSIS Marked enlarged hilar and mediastinal lymph nodes.
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ADENOPATHY DECREASED 2 YRS LATER Lymph nodes are smaller and there is parenchymal lung disease.
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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.
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Diagnosis
Test not always positive
Not used often in US
Test material not approved for sale by FDA.
However, a few hospitals and clinics may have some standardized test preparation prepared privately for their own use
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Prognosis
Good
50% have some permanent organ dysfunction
In 15-20% remains active or recurs intermittently.
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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.
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Treatment
Chloroquine Effectiveness ?
D-penicillamine Effectiveness ?
Chlorambucil
Azathioprine
Methotrexate might suppress alveolitis
Cyclophosphamide may suppress alveolitis
suppress alveolitis by killing the cells that produce granulomas, have also been used
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Treatment
Risk of drugs high, in pregnant women.
Cyclosporine, evaluated in one controlled trial was found unsuccessful.
Cyclosporine, a drug used widely in organ transplants to suppress immune reaction,
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God
Bless
America
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