sarcoidosis

Sarcoidosis

Sarcoidosis• Sarcoidosis is a multisystem

disorder characterized by the presence of noncaseating granulomas.

• 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

Incidence and Prevalence

• Disease can affect people of any age, race and gender.

• 20 to 40 years of age.• Most cases are Sporadic . 5 % of

patients – FH of Sarcoidosis.

Pathophysiology

• Granulomas are Pathologic hall mark of sarcoidosis.

• Granuloma is an organized collection of macrophages.

• granulomas form in response to antigens that are resistant to "first-responder" inflammatory cells such as neutrophils and eosinophils.

• The antigen causing the formation of a granuloma is most often an infectious pathogen or environmental agent, but often the offending antigen is unknown

The antigenic triggering agents cause activation of the Helper T-cell and Macrophages

• Activated Helper T-cell and Macrophages produce IL-2,IFN and TNF complex interaction of cytokines Inflammatory response leading to granuloma

• Giant cells in the central part of the granuloma.

• Giant cells are fused Macrophages-Langerhans giant cells.

• The central epithelioid and giant cells are surrounded by a rim of lymphocytes, mostly T-helper cells

• All granulomas, regardless of cause, may contain additional cells and matrix. These include lymphocytes, neutrophils, eosinophils, fibroblasts and collagen [fibrosis].

CYTOPLASMIC INCLUSION BODY Schaumann body (arrow) is common in

sarcoidosis but is nonspecific.

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 NECROSISCellular 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• 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

LUPUS PERNIO

RAISED PLAQUESThese 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

Musculoskeletal

• Acute polyarthritis with fever is common

• Arthritis is self limited• Chronic destructive bone disease

with deformity is rare• 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.

NASAL BONE LESION Nasal sarcoidosis can lead to osteolysis of

the nasal bone (arrows).

Heart

• 25% have cardiac involvement.• Sarcoidosis can affect any part of the

heart. • Mostly Asymtomatic.• Screening should be done to rule out

cardiac involvement in Sarcoidosis.

Cardiac Sarcoidosis

• Arrhythmias• Heart blocks- common• Heart failure- Restrictive to Dilated CMP.• Pericarditis- Effusions.• MI• SCD

Cardiac Sarcoidosis

• Difficult to Dx.• Screening and Dx can be done by :• ECG ,Holter monitoring ,ECHO• Nuclear imaging (with thallium and/or

technetium sestamibi) • Cardiac PET/MRI • Heart biopsy, rarely /Never-can miss Dx –

patchy involvement of myocardium.

CNS

• Neurosarcoidosis affects 15 percent of sarcoidosis patients. 

• Some people with neurosarcoidosis will recover completely.  In others, sarcoidosis and related nervous system symptoms are chronic, lasting a long time or even a lifetime

• nerve inflammation and damage • peripheral neuropathy • Granulomas in the meninges (or more

rarely in the brain) can lead to meningitis, hydrocephalus and neuroendocrine disorders .

• 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

MR IMAGE Temporal lobe sarcoid lesion (arrow)

Nervous System

• Optic nerve dysfunction-Blurring,double vision,blindness.

• seizures• Paresthesias• Encephalopathy

• CNS symptoms are not usually the first or only sign of sarcoidosis.

• Rarely Neurosarcoidosis is the only sign of sarcoidosis. 

• Isolated Neurosarcoidosis – Difficult to diagnose

• CT/MRI/PET SCAN/LP will aid in Dx.• Biopsy rarely done.

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

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 75-

90% patients including hilar nodes and paratracheal nodes.

• Peripheral lymphadenopathy

Enlarged B/L Hilar, RT paratracheal .

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

• Lymphocytopenia• Mild eosinphilia• Increased E.S.R• Hyperglobulenemia

Lab Abnormalities

• ACE levels elevated 60- 80%.• Activated macrophages produce

ACE.• Non Specific-

Hodgkins,histoplasma,leprosy

• ACE levels tested regularly to check the severity of the disease and to monitor the response to therapy.

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 Permanent lung fibrosis. (20%)

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.

Lung Function Test

• Lung function abnormalities for interstitial lung disease with decreased lung volumes and diffusing capacities

Radiography

• “Egg shell” calcification of hilar nodes• Plural effusions• Cavitations• Atelectasis• Pneumothorax • Cardiomegaly

Lymph nodes with rim (eggshell) calcification (arrow) are rare in sarcoidosis

but common in silicosis.

MOST COMMON PATTERN Bilateral symmetric hilar and right

paratracheal mediastinal adenopathy.

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

Diagnosis

• Identify noncaseating granulomas• 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%

Diagnosis

• KVEIM TEST-Like Mantoux. • 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 • Test material not approved for

sale by FDA.

Differential Diagnosis

1.Hodgkin's disease:

• Mediastinal lymphadenopathy predominates in the anterior mediastinum and the paratracheal regions.

• When lymphadenopathy involves the hilar regions, it is usually asymmetric.

2. Pulmonary tuberculosis:

• Nodal enlargement is unilateral in about 80% of tuberculosis cases.

• Lymph nodes are less well demarcated than in sarcoidosis.

• Lymphadenopathy is almost always associated with ipsilateral lung disease

3.Fungal infections:• Histoplasmosis • Coccidioidomycosis

Lymphadenopathy may be unilateral or bilateral and is usually associated with parenchymal disease. Hilar and/or paratracheal lymph nodes may be involved.

4.Bronchogenic carcinoma:

• Unilateral hilar lymphadenopathy is common.

• The appearance of the primary lung cancer (not visible in all cases) is often a large mass, which is unusual in sarcoidosis.

5.Metastatic lymph node enlargement:

• Primary cancer in the kidney, prostate gland, or the UGI tract usually involves the middle mediastinal lymph nodes.

Prognosis

• Good• In 15-20% remains active or recurs

intermittently. • 50% have some permanent organ

dysfunction

Treatment

• No known cure• Corticosteroids, primary treatment for

inflammation and granuloma formation.• Prednisolone, 1 mg/kg for 4-6 weeks

followed by slow taper over 2-3 months.• Abnormal cardiac/Neuro/Ocular

/Hypercalcemia/Multi system – Steriods must.

Treatment

• Cutaneous Sarcoidosis- Topical steriods/Hydroxychloroquine.

• Hydroxy chloroquine-200-400mg/day-Eye exam -6 monthly.

• MTX- Preni not tolerated/not effective/steriod sparing agent.

• MTX –Start with 10mg/week and maintain with 2.5 to 15mg/week.CBC,KFT,LFT/2months.

Treatment

• Infliximab-Monoclonal Ab to TNF- Improved lung function when given along with predni and MTX- recent RCT.

• Rarely used.• Initial PPD –Reactivation of TB.

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