Sarcoidosis & orphan lung disease

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  • 1.Sarcoidosis & OrphanSarcoidosis & Orphan Lung DiseasesLung Diseases Iman Galal , MDIman Galal , MD Pulmonary Medicine DepartmentPulmonary Medicine Department Ain Shams UniversityAin Shams University

2. Page 2 At The End Of This Lecture You Should Know Who discovered Sarcoidosis? Epidemiology of Sarcoidosis Epidemiology of Sarcoidosis Pathology of Sarcoidosis Pathophysiology of Sarcoidosis Organ involvement in Sarcoidosis Staging of Sarcoidosis How to diagnose Sarcoidosis? How to treat Sarcoidosis? Recommended clinical evaluation of Sarcoidosis How to assess the activity of Sarcoidosis? 3. Page 3 Historical Perspective In 1887, Sir Jonathan Hutchinson was the first to describe a case of cutaneous sarcoid disease. He named the condition "Mortimer's Malady" after the patient. In 1899, Caesar Boeck called this condition 'sarcoid' as he thought it resembles sarcoma. It was called "Boeck's Sarcoid" in his honour. Sir Jonathan HutchinsonSir Jonathan Hutchinson Caesar BoeckCaesar Boeck 4. Page 4 Epidemiology Non-infectious multisystem granulomatous disorder of unknown origin. Female > Male. Black > White. 3rd & 4th decade with 2nd peak at 6th decade. Prevalence rate: 10-40 cases per 100,000. Mortality rate: 1-5 %. 5. Page 5 Etiology Disease of unknown cause. Possible infectious & transmissible cause in genetically susceptible individuals. Possible environmental exposure cause. Possible genetic-environmental interactions. Possible autoimmune cause. 6. Page 6 Pathophysiology of Sarcoidosis 7. Page 7 Pathophysiology of Sarcoidosis T-helper cells to T-suppressor cells ratio is increased in BAL but decreased in peripheral blood. Exaggerated T-cell activity indicates an altered immune response. Hyper globulinemia (Ig A & Ig G). Mass effect of granulomas damages the tissues. 8. Page 8 Pathology of Sarcoidosis 9. Page 9 Pathophysiology of Sarcoidosis Non-caseating epithelioid cell granuloma is the characteristic lesion of sarcoidosis. It occurs along perivascular, peribronchial & septal region areas rich in lymphatic vessels. Granuloma consists of a central collection of modified mononuclear phagocytes called epithelioid cells. Epithelioid cells are mature macrophages that gain secretory & bactericidal capabilities but lose some phagocytic capability. 10. Page 10 Pathophysiology of Sarcoidosis Epithelioid cells are large, polygonal and have an elliptical nucleus which contains fine chromatin & 1-2 nucleoli. Conglomeration of epithelioid cells with multiple peripherally arranged nuclei forms giant cells in the central part of the granuloma. The central epithelioid & giant cells are surrounded by a rim of small, oval, basophilic T-lymphocytes. 11. Page 11 Pathology of Sarcoidosis 12. Page 12 Pathology of Sarcoidosis 13. Page 13 Inclusion Bodies in Sarcoidosis Schaumanns Bodies (Conchoidal Bodies) & Birefringent Crystals: Large, concentrically lamellated, calcified structures that are present within the cytoplasm of giant cells in 88% of cases of sarcoidosis. The majority of Schaumanns bodies have birefringent crystals composed of calcium oxalate. Birefringent crystals may serve as a nidus for their formation. 14. Page 14 Pathology of Sarcoidosis 15. Page 15 Inclusion Bodies in Sarcoidosis Asteroid Bodies: Intracytoplasmic stellate inclusions within giant cells exhibiting 30 or more rays radiating from a central core. They probably represent functionally obsolescent cell organelles. Reported in 2 9 % of sarcoidosis. 16. Page 16 Inclusion Bodies in Sarcoidosis Hamazaki-Wesenberg Bodies: Also known as yellow-brown bodies, yellow bodies, spindle bodies & chromogenic bodies & giant extracellular & intracellular lysosomes. Seen in lymph nodes. They are 0.5 - 0.8 mm oval or spindle shaped, and often exhibit a yellow-brown color. Because they may exhibit an appearance similar to yeast like budding they may be mistaken for fungal organisms. 17. Page 17 Pathology of Sarcoidosis 18. Page 18 Organ Involvement in Sarcoidosis Organ System % of affection Pulmonary > 90 % Psychosocial 30-60 % Ocular 20-30 % Skin 20-30 % Hematologic 20-30 % Endocrine 10-30 % Hepatic/Abdominal 10-20 % Joints & Musculoskeletal 10-20 % Exocrine gland 10-20 % URT & Oral cavity 5-10 % Cardiac 5-10 % Neurological 5-10 % Renal 400 mg/24hr) - Hypercalcemia asymptomatic, 5% - Nephrocalcinosis from chronic hypercalciuria +/- hypercalcemia - Nephrolithiais 10% - Main cause of chronic renal failure 38. Page 41 Renal Sarcoidosis 39. Page 42 Neurosarcoidosis Unilateral or bilateral Bells palsy. Optic neuritis. Multiple or solitary parenchymal mass. May have a ring-like appearance. Mimic glioblastoma or metastases. 40. Page 43 Neurosarcoidosis 41. Page 44 Hematologic Sarcoidosis Lymphadenopathy: cervical, axillary, epitrochlear & supraclavicular. Splenomegly & hypersplenism. Peripheral blood lymphopenia. 42. Page 45 Hepatic Sarcoidosis Dysfunction of these organ is uncommon. Hepatosplenic Sarcodosis: minimal organomegaly & coalescing granulomas. 43. Page 46 Liver & Spleen Sarcoidosis 44. Page 47 GIT Sarcoidosis Most common site: stomach dyspepsia & abdominal pain. Gastric sarcoidosis has predilection for the antrum. Diagnosis requires endoscopic biopsy 45. Page 48 Genital Sarcoidosis Testicular involvement can be associated with Epididymitis and is typically Bilateral & Multiple. Does not affect fertility & does not increase the incidence of fetal or obsterical complications. 46. Page 49 Cardiac Sarcoidosis Clinically evident cardiac sarcoidosis is uncommon, affectingClinically evident cardiac sarcoidosis is uncommon, affecting 2-7% of patients with sarcoidosis. However, occult2-7% of patients with sarcoidosis. However, occult involvement is much higher (> 20%).involvement is much higher (> 20%). Cardiac involvement may occur at any point during the courseCardiac involvement may occur at any point during the course of sarcoidosis, may occur in the absence of pulmonary orof sarcoidosis, may occur in the absence of pulmonary or systemic involvement & may be a presenting feature.systemic involvement & may be a presenting feature. Sarcoidosis can involve any part of the heart, includingSarcoidosis can involve any part of the heart, including myocardium, endocardium & pericardium.myocardium, endocardium & pericardium. Although the disease is often clinically silent, cardiacAlthough the disease is often clinically silent, cardiac sarcoidosis is a leading cause of death among patients withsarcoidosis is a leading cause of death among patients with sarcoidosis, with mortality rate of 50-85%.sarcoidosis, with mortality rate of 50-85%. 47. Page 50 Clinical Manifestations of Cardiac Sarcoidosis Asymptomatic granulomata. Conduction defects (e.g., bundle branch blocks; complete heart block). Atrial arrhythmias. Mitral insufficiency. Ventricular aneurysms. Pericardial effusions; fibrosis. Tachyarrhythmias (ventricular > atrial). Congestive heart failure. 48. Page 51 Cardiac Sarcoidosis Guidelines for Diagnosis of Cardiac Sarcoidosis from Japanese Ministry of Health & Welfare: Cardiac sarcoidosis is diagnosed when histologic analysis of operative or endomyocardial biopsy specimens demonstrates epithelioid granuloma without caseating granuloma Clinical diagnosis group: In patients with histologic diagnosis of extracardiac sarcoidosis, cardiac sarcoidosis is diagnosed when (a) and 1 or more of (be) are present. (a) Complete right bundle branch block, left-axis deviation, atrioventricular block, ventricular tachycardia, premature ventricular contraction (>grade 2 in Lowns classification), or abnormal Q or STT change on electrocardiogram or Holter electrocardiogram (b) Abnormal wall motion, regional wall thinning or thickening, or dilatation of LV on echocardiogram (c) Perfusion defect in 201Tl myocardial scintigram or abnormal accumulation in 67Ga-citrate or 99mTc-pyrophosphate myocardial scintigram (d) Abnormal intracardiac pressure, low cardiac output, or abnormal wall motion or depressed ejection fraction of LV (e) Interstitial fibrosis or cellular infiltration over moderate grade in endomyocardial biopsy even if findings are nonspecific 49. Page 52 Diagnosis Clinical. Radiological (Chest radiograph & Gallium scan). Functional (Spirometry, DLCO & Lung Volumes). Laboratory (CBC with differential count & SACE). Skin tests. Biopsy. ECG. Opthalmological examination. Organ-specific investigations. 50. Page 53 Radiological Staging of Sarcoidosis Scadding's Classification Stage 0=normal Stage 1=Hilar LDN alone Stage 2=Hilar LDN+parenchymal infiltrates Stage 3=Parenchymal infiltrates alone Stage 4=Pulmonary fibrosis Strong predilection for theStrong predilection for the Upper LungUpper Lung 51. Page 54 Gallium 67 Scan Lung gallium scan is a type of nuclear scan involving radioactive gallium (Ga.). The test helps determine whether a patient has inflammation in the lungs. Gallium is injected IV. The scan will be taken 6-24 hrs after the gallium is injected. (time depends on whether the condition is acute or chronic ). During the test, you lie on a table that moves underneath a scanner called a gamma camera. The camera detects the rays emitted by the gallium. 52. Page 55 Gallium 67 Scan 53. Page 56 Serum Angiotensin Converting Enzyme (SACE) SACE is the most widely used test in the follow-up of sarcoidosis patients. It is a membrane bound glycoprotein found in Activated Alveolar Macrophages & at the surface of Epithelioid cells & consequently may reflect development & extent of granulomas. It may be normal in early & acute disease reflecting the small number of granulomas present at this stage. It is poorly correlated with pulmonary function & variably related with radiogra