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Approach to vasculitis

Assistant Professor (Pathology) um Fatima Memorial College of Medicine & Dentistry
28. May 2018
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Approach to vasculitis

  1. APPROACH TO VASCULITIS Dr. Muhammad Usman Shams
  2. ( Glycosaminoglycan = Amino sugar + Polysaccharide ) NORMAL BLOOD VESSEL  The basic constituents of the walls of blood vessels are  Endothelial cells (ECs)  Smooth muscle cells  Extracellular matrix: elastin, collagen, & glycosaminoglycans (GAG).  The three concentric layers, intima, media and adventitia are most clearly defined in larger vessels particularly arteries. Intima Elastica interna Inner 1/3rd media Outer 2/3rd media Adventitia Coronary Artery Structure Vasa Vasorum
  3.  Arteries are divided into three types based on their size and structure.  Large (or elastic) Arteries: Aorta and its major branches (innominate, subclavian, common carotid & iliac) & Pulmonary arteries.  Medium (or Muscular) Arteries (Coronary & renal)  Small Arteries (less than 2 mm)  Arterioles (20 to 100 µm in diameter)  Capillaries (7 to 8 µm)
  4.  Elastic arteries have rich component of elastic fibers in addition to smooth muscle allow them to expand during systole and propel blood onwards with elastic recoil during diastole.  Muscular Arteries have no elastic fibers in the media and only have elastica interna and externa. The muscle fibers have circular & spiral arrangement in the media. These regulate blood flow by contraction and dilation of lumina; and are controlled by autonomic nervous system and/or local control by cellular secretions).
  5. Small muscular Artery Vein The Vascular Wall Histologic section containing a portion of an artery and adjacent vein. Elastic membranes are stained black. Because it is exposed to higher blood pressures, the artery has a thicker wall that maintains an open, round lumen, even when blood is absent. Moreover, the elastin of an artery is more organized than in the corresponding vein. The vein has a larger, but collapsed, lumen, and the elastin in the wall is diffusely distributed.
  6. VASCULITIS A clinicopathologic process characterized by inflammation of and damage to blood vessels, often resulting in complete or partial occlusion of the involved vessels, with resulting ischemic damage to the supplied organ/tissue.  Fairly rare diseases  Presentation: highly variable making delays in diagnosis common  High morbidity and mortality  Therapeutic challenge often requiring prolonged & intensive immunosuppression.
  7. CLASSIFICATION (Cause)  Primary vasculitis – occurs in absence of recognized precipitating cause/associated disease  Secondary vasculitis  secondary to established disease  secondary to infection  secondary to malignancy  secondary to drugs
  8. CLASSIFICATION (Vessel Size)  Large vessel vasculitis  Giant cell arteritis  Takayasu’s arteritis  Medium-sized vessel vasculitis  Polyarteritis nodosa  Kawasaki’s disease  Primary granulomatous CNS vasculitis  Small vessel vasculitis  ANCA associated vasculitis  Immune complex small vessel vasculitis  Paraneoplastic small vessel vasculitis  Inflammatory bowel disease vasculitis
  9. Small Vessel Vasculitis  ANCA associated  Microscopic polyangiitis  Wegeners’s granulomatosis  Churg-Strauss syndrome  Drug induced ANCA associated vasculitis – PTU and hydralazine  Immune complex  Cryoglobulinemic vasculitis  Henoch-Schonlein purpura  Lupus vasculitis  Urticarial vasculitis  Goodpasture’s syndrome  Serum-sickness vasculitis  Drug induced immune complex vasculitis  Paraneoplastic  Lymphoproliferative/Myeloproliferative/Carcinoma induced vasculitis
  10. PATHOGENESIS  Remains largely unknown  Two possible mechanisms: (Most likely multifactorial)  Infectious  Non-infectious
  11. INFECTIOUS VASCULITIS  Caused by the direct invasion of infectious agents, usually bacteria or fungi, and in particular Aspergillus and Mucor species.  Vascular invasion can be  part of a localized tissue infection (e.g., bacterial pneumonia or adjacent to abscesses) OR  from hematogenous seeding of bacteria during septicemia or embolization from sepsis of infective endocarditis. (less common)  Vascular infections can weaken arterial walls and culminate in mycotic aneurysms, or can induce thrombosis and infarction.
  12. NON-INFECTIOUS VASCULITIS  The main immunological mechanisms that initiate noninfectious vasculitis are  Immune complex deposition  Antineutrophil cytoplasmic antibodies (ANCA)  Anti–endothelial cell antibodies.
  13. Immune Complex Deposition  Antibody and complement are typically detected in vasculitic lesions or/and in circulation. _________________  Systemic immunological diseases, such as systemic lupus erythematosus (SLE) and polyarteritis nodosa.  Drug hypersensitivity: In some cases (e.g., penicillin) the drugs bind to serum proteins; other agents, like streptokinase, are themselves foreign proteins.  Secondary to viral infections: Antibody to viral proteins forms immune complexes that can be found in the serum and the vascular lesions.
  14. ANCA  Anti-Neutrophil Cytoplasmic Antibodies  Ab directed against proteins in the cytoplasmic granules of PMN’s and monocytes  Seen in  Wegener’s Granulomatosis (PR3)  Microscopic Polyangiitis (MPO)  Churg-Strauss (MPO)  Crescentic/necrotizing GN
  15. c-ANCA  Serum from patients bind to cytoplasmic granules and show a granular appearance on immunofluorescence  Proteinase-3 (PR-3) is the major antigen.  serine protease  present in azurophilic granules p-ANCA  Localized, peri-nuclear staining pattern on PMN’s  Myeloperoxidase (MPO) is the major target.  normally involved in generating oxygen free radicals  present in lysozomes
  16.  A plausible mechanism for ANCA vasculitis is the following:  Drugs or cross-reactive microbial antigens induce ANCAs.  Neutrophil surface expression or release of PR3 and MPO (e.g., in the setting of infections) incites ANCA formation in a susceptible host.  Subsequent infection, endotoxin exposure, or other inflammatory stimuli elicit cytokines such as TNF that cause surface expression of PR3 and MPO on neutrophils and other cell types.  ANCAs react with these cytokine-activated cells and either cause direct injury (e.g., to endothelial cells) or induce further activation (e.g., in neutrophils).  ANCA-activated neutrophils degranulate and also cause injury by releasing reactive oxygen species, engendering endothelial cell toxicity and other indirect tissue injury.
  17. Anti-Endothelial Cell Antibodies  Antibodies to endothelial cells may predispose to certain vasculitides, for example, Kawasaki disease.
  18. SYSTEMIC MANIFESTATIONS
  19. LAB INVESTIGATIONS
  20. Assessing Inflammation  CBC  leucocytosis consistent with infection & primary vasculitis  leucopaenia associated with CTDs  eosinophils - elevated in CSS and drug reaction  ESR/CRP
  21. Assessing Organ Damage  Liver function  LFTs – May suggest viral infection  Urine analysis  Proteinuria  Haematuria  Casts  Renal function  Creatinine clearance  24hr protein excretion  Biopsy  Chest radiograph  Nervous system  Angiography  Cardiac function  ECG  Echo  Gut  Angiography
  22. Assessing Immune Mechanisms  Anti-neutrophil cytoplasmic antibodies  Rheumatoid factor  ANA nuclear antibodies  Anti dsDNA  Anticardiolipin  Complement  Levels are low in SLE and infection but high in primary vasculitis  Cryoglobulins
  23. Specific  Imaging of sinuses  Biopsy of affected organs e.g. skin/kidney/temporal artery– necessary to confirm diagnosis  ANCA  Viral Serology
  24. Vasculitis Affected organs Histopathology Cutaneous small-vessel vasculitis Skin, kidneys Neutrophils, fibrinoid necrosis Wegener's granulomatosis Nose, lungs, kidneys Neutrophils, giant cells Churg–Strauss syndrome Lungs, kidneys, heart, skin Histiocytes, eosinophils Kawasaki disease Skin, heart, mouth, eyes Lymphocytes, endothelial necrosis Buerger's disease Leg arteries and veins (gangrene) Neutrophils, granulomas
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