Vasculitis classification, secondary forms, mimickers

Very under-diagnosed entity, covers the doubtful grey areas as well.

1. Vasculitis- Classification, secondary forms, mimickers Dr. Shinjan Patra

2. Introduction Vasculitis- A clinico -pathologic process characterized by inflammation of and damage to blood vessels. Vessel lumen is usually compromised and associated with ischemia of the tissues. May be the sole manifestation of a disease or may be a secondary component.

3. When to Suspect a Vasculitis Unexplained ischemia: Claudication, limb ischemia, angina, TIA, stroke, mesenteric ischemia, cutaneous ischemia Especially in a young individual

4. Multi-organ dysfunction Suggestive features: Glomerulonephritis Peripheral neuropathy Pulmonary hemorrhage Sub-acute endocarditis Skin manifestations- purpura, urticaria, livedo reticularis, vesiculo-bullous lesions.

5. Classification Primary Vasculitis syndromes- Vasculitis is the principal feature of the disease. Secondary vasculitis syndromes- Vasculitis is a secondary manifestation of a connective tissue disorder.

6. Primary Vasculitis syndromes Predominantly Large Vessel (Aorta and its major branches & corresponding vessel in venous circulation)- Giant cell arteritis Takayasu’s arteritis Cogan’s syndrome Behcet’s disease

7. Predominantly Medium Vessel vasculitis- smaller than major aortic branches, yet enough to contain four elements (intima, elastic lamina, media, adventitia) Polyarteritis Nodosa Kawasaki’s disease Buerger’s disease Primary angitis of CNS

8. Predominantly Small Vessel vasculitis (includes capillaries, post-capillary venules, arterioles- less than 500 μ in outer diameter) Immune Complex mediated- Good-pasture’s disease, HSP, cutaneous leucocytoclastic angitis, essential cryoglobulinemia. ANCA-associated disorders- Granulomatosis with polyangitis , Microscopic polyangitis, Churg -Strauss syndrome.

9. Primary Vasculitis syndromes

10. Comparison of predominant C/F in these groups- Large-vessel vasculitis Medium-vessel vasculitis Small-vessel vasculitis Limb Claudication Cutaneous nodules + ulcers Purpura + urticaria Asymmetric blood pressures Digital gangrene Glomerulonephritis Absence/ Inequality of pulses Mononeuritis multiplex Alveolar hemorrhage Bruits Renovascular hypertension Uveitis/ scleritis/ splinter hemorrhages

11. Pathophysiologic mechanisms Pathogenic immune complex deposition- Lupus vasculitis, Hep -C/ hep -B asso vasculitis. Production of anti-neutrophilic cytoplasmic antibodies- Granulomatosis with polyangitis, microscopic polyangitis, churg-strauss syn. Pathogenic T-lymphocyte responses and granuloma formation- Giant cell arteritis, Takayasu’s arteritis.

12. ANCA- Anti-Neutrophilic Cytoplasmic Antibodies Antibodies directed against neutrophil granule constituents c-ANCA Stains cytoplasm (hence “c”) Main target antigen: proteinase-3 Highly specific (>90%) for Wegener’s p-ANCA Stains perinuclear (hence “p”) Main target antigen: myeloperoxidase A/w MPA and Churg -Strauss

13. Secondary Vasculitis syndromes Specific etiology- Drug-induced Hep -C associated cryoglobulinemic vasculitis Hep -B associated vasculitis Malignancy associated Associated with systemic disease- Lupus vasculitis Rheumatoid vasculitis Sarcoid vasculitis

14. Drug Induced vasculitis Examples- Hydralazine, propyl-thiouracil, Allopurinol, Thiazides, Gold, Sulfonamides, Phenytoin, Penicillin. Palpable purpura- generalized/ limited to lower extremities/ urticarial lesions/ hemorrhagic blisters. Glomerulonephritis/ pulmonary hemorrhage. T/t- Glucocorticoids/ Cyclophosphamide

15. Hep -C associated cryoglobulinemic vasculitis Type 2 & 3 cryoglobulinemia- monoclonal/polyclonal IgG and IgM . C/f- fatigue, arthralgia’s, purpura, raynaud’s phenomenon, peripheral neuropathy & nephropathy. T/t- Antivirals + Rituximab + low-dose IL-2

16. Hep -B associated Vasculitis Associated with polyarteritis nodosa Type 2 & 3 cryoglobulinemic vasculitis- fatigue, arthralgia’s, purpura, raynaud’s phenomenon, peripheral neuropathy & nephropathy. T/t- Tenofovir/ Entacavir.

17. RA associated vasculitis Incidence- less than 1% + hypocomplementemia C/f- petechiae, purpura, digital infarcts, gangrene, livedo reticularis, painful lower extremity ulcers, sensorimotor polyneuropathy. Bywater’s lesion- Isolated digital vasculitis with splinter like lesions in peri-ungual region. T/t- Usual DMARD’s + cyclophosphamide + CS

18. Lupus associated vasculitis Vasculitic rash in 20% of cases. Ischemic events- TIA, CVA, AMI. Associated atherosclerosis and dyslipidemia. T/t- Immunosuppressive + statins.

19. Paraneoplastic peripheral neuropathies Painful symmetric or asymmetric distal axonal sensorimotor neuropathy. SCLC & lymphoma- commonest. T/t- CS + cyclophosphamide.

20. Vasculitis Mimickers Infectious disease- Bacterial endocarditis- Janeway lesions, septic emboli with hemorrhage & infarction. Disseminated Gonococcal infection- Petechial lesions/ papular lesions/ pustular lesions. Pulmonary Histoplasmosis Coccidioidomycosis Whipple’s disease

21. Syphilis- Lyme disease Rocky mountain spotted fever Neoplasms - Atrial myxomas Lymphoma Carcinomatosis

22. Coagulopathies- Antiphospholipid syndrome Thrombotic/ Immune thrombocytopenic purpura Warfarin induced skin necrosis DIC Drug toxicities- Cocaine Levamisole Amphetamines Others- Sarcoidosis, Amyloidosis, Migraine.

23. Thank you