Copyright Thorax.us 2005 Ramesh Kaul,MD Sarcoidosis Ramesh Kaul, MD,MS,FCCP Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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 Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD Etiology Results from exaggerated cellular immune response (acquired, inherited or both) to a limited class of antigens or self antigens. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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) Copyright Thorax.us 2005 Ramesh Kaul,MD

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 Copyright Thorax.us 2005 Ramesh Kaul,MD

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 Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD Pathophysiology Accumulation of mononuclear inflammatory cells and T helper lymphocytes Formation of granulomas, aggregates of macrophages, epithelioid cells and multinucleated giant cells Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD LANGHANS' GIANT CELL Langhans' giant cell in center of granuloma is surrounded by epithelioid cells . Note peripherally arranged nuclei in giant cell. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD ADVANCED COLLAGENOUS FIBROSIS Elongated fibroblasts (FB) with extensive collagenous tissue (C). Giant cells (arrows) Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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 Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD CYTOPLASMIC INCLUSION BODY Schaumann body (arrow) is common in sarcoidosis but is nonspecific. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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. Copyright Thorax.us 2005 Ramesh Kaul,MD

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 Copyright Thorax.us 2005 Ramesh Kaul,MD

Clinical Manifestations Respiratory symptoms are most common Cough, chest discomfort, and dyspnea Symptoms reflect the specific organs involved by the granulomas Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD Noncaseating granuloma in lung is the characteristic lesion of sarcoidosis. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD CASEOUS NECROSIS Cellular destruction in TB granuloma appears as clumped debris (arrows). This necrosis does not occur in sarcoidosis. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD M. tuberculosis BACILLI Caseous necrosis is most common in TB, but Gram negative, acid fast bacilli must be identified to make the diagnosis. Copyright Thorax.us 2005 Ramesh Kaul,MD

SUBPLEURAL GRANULOMA IN LUNG Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD CONJUNCTIVITIS Copyright Thorax.us 2005 Ramesh Kaul,MD

PAPILLEDEMA Often associated with 7th nerve facial palsy. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD NAKED GRANULOMA Young granulomas (arrows) in the skin with no surrounding rim of mononuclear cells. Copyright Thorax.us 2005 Ramesh Kaul,MD

ERYTHEMA NODOSUM These reddish raised lesions. Lesions resolve spontaneously in weeks. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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 Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD LUPUS PERNIO Facial lesions are most common, but the extremities and buttocks can be involved. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD LUPUS PERNIO Indurated and violaceous range from a few small lesions to large lesions Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD SMALL NODULES Papules and nodular lesions, can be found anywhere on the body. Papules are often multiple while nodules are often solitary. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD RAISED PLAQUES These raised plaques are the result of coalescence of nodules. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD PSORIASIS LIKE LESIONS These small white lesions closely resemble psoriasis. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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 Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD SPLEEN & LIVER GRANULOMAS The small low attenuation lesions in the liver and spleen in sarcoidosis. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD EARLY COLLAGEN FORMATION Extracellular collagen (C) is being produced by fibroblasts Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD PUNCHED OUT LYTIC LESIONS Focal osteolytic lesions in the fingers are most common abnormality. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD LACY TRABECULAR PATTERN Osteolysis has left a lacy trabecular pattern in this phalanx (arrow) Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD DEFORMING LESIONS Advanced sarcoidosis with osteolytic lesions of the distal forearm, wrist, and bones of the hand Copyright Thorax.us 2005 Ramesh Kaul,MD

SCLEROTIC LESION Rare and often in the axial skeleton. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD SCLEROTIC LESIONS, NONSPECIFIC Focal sclerosis (arrows) of distal phalanges is unusual Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD NASAL BONE LESION Nasal sarcoidosis can lead to osteolysis of the nasal bone (arrows). Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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 Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD T1-W POST GADOLINIUM MR IMAGE Post contrast image of high signal intensity temporal lobe sarcoid lesion (arrow) Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD T2-W MR IMAGE High signal intensity edema surrounding biopsy proven sarcoid lesion. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD Nervous System Optic nerve dysfunction Papilledema Palate dysfunction Hearing abnormalities Paresthesias Meningeal granulomas Encephalopathy Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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 Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD NEPHROCALCINOSIS There are multiple calcifications of the kidneys. Enlarged retroperitoneal lymph nodes (arrows) Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD Kidney Increased calcium absorption in the gut Related to high levels of circulating 1,25-dihydroxy vitamin D produced by mononuclear phagocytes in granulomas Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD Lymph Nodes Lymphadenopathy Intrathoracic nodes enlarged in 75-90% patients including hilar nodes and paratracheal nodes. Peripheral lymphadenopathy Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD Enlarged bilateral hilar, right paratracheal (arrow), and aortopulmonary window (arrowhead) nodes. Copyright Thorax.us 2005 Ramesh Kaul,MD

CALCIFIED LYMPH NODES late manifestation in 5% of patients. Copyright Thorax.us 2005 Ramesh Kaul,MD

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 Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD ABDOMINAL LYMPHADENOPATHY Multiple enlarged paraaortic, paracaval, and porta hepatis lymph nodes (arrows). Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD GASTRIC SARCOID Granuloma involves the gastric antrum leading to irregular nonspecific narrowing. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD COLONIC SARCOID Irregular narrowing of the rectosigmoid has the appearance of inflammatory disease or malignancy. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD Lab Abnormalities Lymphocytopenia Mild eosinphilia Increased E.S.R Hyperglobulenemia Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD Lab Abnormalities Elevated level of angiotensin converting enzyme Gallium 67 lung scan showing a pattern of diffused uptake. Bronchiole alveolar lavage shows increased lymphocytes Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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. Copyright Thorax.us 2005 Ramesh Kaul,MD

STAGE I Thoracic lymphadenopathy. Normal lung parenchyma. (50%) Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD STAGE II Hilar and mediastinal lymphadenopathy. Abnormal lung parenchyma. ( 30% ) Copyright Thorax.us 2005 Ramesh Kaul,MD

STAGE III Abnormal lung parenchyma. No lymphadenopathy. ( 15% ) Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD STAGE IV Extensive pulmonary fibrosis is typically worst in the upper lobes. Copyright Thorax.us 2005 Ramesh Kaul,MD

STAGE IV Broad bands of fibrosis in the upper lobes. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD ALVEOLAR SARCOIDOSIS Multiple lung masses are an unusual form of sarcoidosis, resembles lung metastases. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD CAVITARY SARCOIDOSIS Rare pattern of multiple cavitary sarcoid lung lesions. Note lymphadenopathy. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD RETICULONODULAR PATTERN Common appearance of sarcoidosis involving the lung parenchyma. Note enlarged hilar lymph nodes. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD RETICULONODULAR PATTERN CLOSEUP Well defined linear and nodular densities characteristic of lung interstitial disease. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD ACINAR PATTERN Poorly defined nodular opacities are the size of pulmonary acini (6mm). Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD PNEUMONIC APPEARANCE Confluent acinar opacities look similar to pneumonic consolidation. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD NODULAR PATTERN Small 5mm nodules are subpleural, along fissures and bronchovascular bundles. Give the vessels (arrow) and fissures a beaded appearance. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD Lung Function Test Lung function abnormalities for interstitial lung disease with decreased lung volumes and diffusing capacities Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD Radiography “Egg shell” calcification of hilar nodes Plural effusions Cavitations Atelectasis Pulmonary hypertension Pneumothorax Cardiomegaly Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD Lymph nodes with rim (eggshell) calcification (arrow) are rare in sarcoidosis but common in silicosis. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD MOST COMMON PATTERN Bilateral symmetric hilar and right paratracheal mediastinal adenopathy. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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. Copyright Thorax.us 2005 Ramesh Kaul,MD

STAGE IV Permanent lung fibrosis. (20%) Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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 Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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% Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD ADENOPATHY AT TIME OF DIAGNOSIS Marked enlarged hilar and mediastinal lymph nodes. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD ADENOPATHY DECREASED 2 YRS LATER Lymph nodes are smaller and there is parenchymal lung disease. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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 Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD Prognosis Good 50% have some permanent organ dysfunction In 15-20% remains active or recurs intermittently. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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. Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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 Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD 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, Copyright Thorax.us 2005 Ramesh Kaul,MD

Copyright Thorax.us 2005 Ramesh Kaul,MD God Bless America Copyright Thorax.us 2005 Ramesh Kaul,MD