Sarcoidosis is a multisystem disorder characterized by the formation of noncaseating granulomas in multiple organs. It most commonly involves the lungs, lymph nodes, skin, and eyes. The cause is unknown but believed to be due to an abnormal immune response to unknown antigens in genetically predisposed individuals. Diagnosis is based on clinical features and identification of granulomas on biopsy, and exclusion of other conditions. While often asymptomatic, it can cause respiratory symptoms as well as involvement of other organs. Treatment involves corticosteroids, with hydroxychloroquine or methotrexate as steroid-sparing options. Prognosis is generally good, though some degree of permanent organ dysfunction occurs in about half of

1. Sarcoidosis

2. SarcoidosisSarcoidosis is a multisystem disorder characterized by the presence of noncaseatinggranulomas.Most affected organ is the lungSkin, eyes and lymph nodes are frequently involvedAcute or sub acute and self limitingWaxing and waning over years

3. Incidence and PrevalenceDisease can affect people of any age, race and gender.

4. 20 to 40 years of age.

5. Most cases are Sporadic . 5 % of patients – FH of Sarcoidosis.PathophysiologyGranulomas are Pathologic hall mark of sarcoidosis.Granuloma is an organized collection of macrophages.

6. 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

7. 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 granulomaGiant cells in the central part of the granuloma.

8. 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

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

10. CYTOPLASMIC INCLUSION BODY Schaumann body (arrow) is common in sarcoidosis but is nonspecific.

11. Clinical Manifestations50% patients are asymptomaticAbnormal "routine" chest radiographSymptomatic patients, with wide variety of symptomsOnset is usually insidious but can be acute

12. Clinical ManifestationsRespiratory symptoms are most commonCough, chest discomfort, and dyspnea Symptoms reflect the specific organs involved by the granulomas

13. LungsFirst site involvedBegins with alveolitis involving small bronchi and small blood vessels Alveolitis either clears up spontaneously or leads to granuloma Fibrosis

14. Noncaseating granuloma in lung is the characteristic lesion of sarcoidosis.

15. CASEOUS NECROSISCellular destruction in TB granuloma appears as clumped debris (arrows). This necrosis does not occur in sarcoidosis.

16. M. tuberculosis BACILLI Caseous necrosis is most common in TB, but Gram negative, acid fast bacilli must be identified to make the diagnosis.

17. SUBPLEURAL GRANULOMA IN LUNG

18. Eyes25% have eye lesionsBlurred vision, pain, photophobia and dry eyesChronic uveitis leads to glaucoma, cataracts and blindness Keratoconjunctivitis siccaPapilledema

19. CONJUNCTIVITIS

20. PAPILLEDEMA Often associated with 7th nerve facial palsy.

21. Skin33% have skin lesionsLOFGREN'S SYNDROME; acute triad of erythemanodosum, joint pains, and bilateral hilaradenopathy

22. NAKED GRANULOMA Young granulomas (arrows) in the skin with no surrounding rim of mononuclear cells.

23. ERYTHEMA NODOSUM These reddish raised lesions.

24. SkinLupus pernio- indurated blue purple swollen shiny lesions on nose, cheeks, lips, ears and fingers. Papules, nodules, and plaques Psoriatic like lesions

25. LUPUS PERNIO

26. RAISED PLAQUESThese raised plaques are the result of coalescence of nodules.

27. PSORIASIS LIKE LESIONS These small white lesions closely resemble psoriasis.

28. Liver33% have hepatomegaly or biochemical evidence of disease Symptoms usually absentCholestasis, fibrosis, cirrhosis, portal hypertension, and the Budd-Chiari syndrome have been seen

29. MusculoskeletalAcute polyarthritis with fever is commonArthritis is self limitedChronic destructive bone disease with deformity is rareMuscle disease is rare

30. PUNCHED OUT LYTIC LESIONS Focal osteolytic lesions in the fingers are most common abnormality.

31. LACY TRABECULAR PATTERN Osteolysis has left a lacy trabecular pattern in this phalanx (arrow)

32. DEFORMING LESIONS Advanced sarcoidosis with osteolytic lesions of the distal forearm, wrist, and bones of the hand

33. SCLEROTIC LESION Rare and often in the axial skeleton.

34. NASAL BONE LESION Nasal sarcoidosis can lead to osteolysis of the nasal bone (arrows).

35. Heart25% have cardiac involvement.Sarcoidosis can affect any part of the heart.Mostly Asymtomatic.Screening should be done to rule out cardiac involvement in Sarcoidosis.

36. Cardiac SarcoidosisArrhythmiasHeart blocks- commonHeart failure- Restrictive to Dilated CMP.Pericarditis- Effusions.MISCD

37. Cardiac SarcoidosisDifficult to Dx.Screening and Dx can be done by :ECG ,Holter monitoring ,ECHONuclear imaging (with thallium and/or technetium sestamibi) Cardiac PET/MRI Heart biopsy, rarely /Never-can miss Dx –patchy involvement of myocardium.

38. CNSNeurosarcoidosis 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

39. 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 involved7th nerve facial palsy is most commonAcute, transient, and can be unilateral or bilateralHEREFORDT'S SYNDROME; facial palsy accompanied by fever, uveitis, and enlargement of the parotid gland

40. MR IMAGE Temporal lobe sarcoid lesion (arrow)

41. Nervous SystemOptic nerve dysfunction-Blurring,doublevision,blindness.seizuresParesthesiasEncephalopathy

42. CNS symptoms are not usually the first or only sign of sarcoidosis.Rarely Neurosarcoidosis is the only sign of sarcoidosis. Isolated Neurosarcoidosis – Difficult to diagnoseCT/MRI/PET SCAN/LP will aid in Dx.Biopsy rarely done.

43. KidneyGranulomatous interstitial nephritis produces renal failureDevelops over a period of weeks to monthsRapid response to steroid therapyKidney stones (nephrolithiasis) and nephrocalcinosis are very unusual secondary to hypercalcemia and hypercalciuria

44. KidneyIncreased calcium absorption in the gutRelated to high levels of circulating 1,25-dihydroxy vitamin D produced by mononuclear phagocytes in granulomas

45. Lymph NodesLymphadenopathyIntrathoracic nodes enlarged in 75-90% patients including hilar nodes and paratracheal nodes. Peripheral lymphadenopathy

46. Enlarged B/L Hilar, RT paratracheal .

47. CALCIFIED LYMPH NODES late manifestation in 5% of patients.

48. PARACARDIAC LYMPH NODE

49. ABDOMINAL LYMPHADENOPATHY Multiple enlarged paraaortic, paracaval, and porta hepatis lymph nodes (arrows).

50. GASTRIC SARCOID Granuloma involves the gastric antrum leading to irregular nonspecific narrowing.

51. COLONIC SARCOID Irregular narrowing of the rectosigmoid has the appearance of inflammatory disease or malignancy.

52. Lab AbnormalitiesLymphocytopeniaMild eosinphiliaIncreased E.S.RHyperglobulenemia

53. Lab AbnormalitiesACE levels elevated 60- 80%.

54. Activated macrophages produce ACE.

55. Non Specific-Hodgkins,histoplasma,leprosy

56. ACE levels tested regularly to check the severity of the disease and to monitor the response to therapy.RadiographyCXR 3 classic patterns are seen. Type 1- bilateral hilaradenopathy with no parenchymal abnormalities. Type 2- bilateral hilaradenopathy with diffused parenchymal changes. Type 3- diffused parenchymal changes without hilaradenopathy.

57. STAGE I Thoracic lymphadenopathy. Normal lung parenchyma. (50%)

58. STAGE II Hilar and mediastinal lymphadenopathy. Abnormal lung parenchyma. ( 30% )

59. STAGE III Abnormal lung parenchyma. No lymphadenopathy. ( 15% )

60. STAGE IV Permanent lung fibrosis. (20%)

61. MILIARY SARCOIDOSIS CT shows well defined lung nodules less than 5mm in diameter. This pattern is rare.

62. ALVEOLAR SARCOIDOSIS Multiple lung masses are an unusual form of sarcoidosis, resembles lung metastases.

63. Lung Function TestLung function abnormalities for interstitial lung disease with decreased lung volumes and diffusing capacities

64. Radiography“Egg shell” calcification of hilar nodesPlural effusionsCavitationsAtelectasisPneumothoraxCardiomegaly

65. Lymph nodes with rim (eggshell) calcification (arrow) are rare in sarcoidosis but common in silicosis.

66. MOST COMMON PATTERN Bilateral symmetric hilar and right paratracheal mediastinal adenopathy.

67. DiagnosisDifficult to differentiate from chronic infections, fungal diseases, T.B. and lymphoma. Based on combined clinical, radiologic and histologic findings. Laboratory tests seldom important

68. DiagnosisIdentify noncaseatinggranulomasTransbronchial biopsies positive in 65-95%, even if no lung parenchymal abnormalities imaged. Tissue from mediastinoscopy positive in 95%Scalene node biopsy positive in 80%

69. DiagnosisKVEIM 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.

70. DiagnosisTest not always positive Test material not approved for sale by FDA.

71. Differential Diagnosis1.Hodgkin's disease: Mediastinal lymphadenopathy predominates in the anterior mediastinum and the paratracheal regions. When lymphadenopathy involves the hilar regions, it is usually asymmetric.

72. 2. Pulmonary tuberculosis: Nodal enlargement is unilateral in about 80% of tuberculosis cases.

73. Lymph nodes are less well demarcated than in sarcoidosis.

74. Lymphadenopathy is almost always associated with ipsilateral lung disease3.Fungal infections:Histoplasmosis

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

76. 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.

77. 5.Metastatic lymph node enlargement: Primary cancer in the kidney, prostate gland, or the UGI tract usually involves the middle mediastinal lymph nodes.

78. PrognosisGoodIn 15-20% remains active or recurs intermittently. 50% have some permanent organ dysfunction