Vasculitis Update 2013

1. Vasculitis Update 2013 William E Davis, MD, FACP

2. Classification • Large vessel disease • Takayasu’sarteritis • Giant cell arteritis (temporal arteritis) • Cogan’s syndrome • Behcet’s disease • Medium vessel disease • Polyarteritisnodosa • Buerger’s disease • Kawasaki disease • Primary angiitis of the central nervous system

3. Classification • Small vessel vasculitis • Immune complex mediated • Anti-glomerular basement membrane disease (Goodpasture’s) • Cutaneousleukocytoclasticvasculitis • HenochSchonleinpurpura • Hypocomplementemicurticarialvasculitis • Essential cryoglobulinemia • Erythemaelevatumdiutinum • ANCA-associated disorders • Granulomatosis with polyangiitis ( Wegener’s) • Microscopic polyangiitis • Churg-Strauss syndrome

4. Giant Cell Arteritis • Temporal Arteritis • Age > 50 • Extracranial branches of carotid arteries • HLA DRB1*04 • Polymyalgiarheumatica

5. Giant Cell Arteritis • Clinical features • Age > 50 • New onset headache or cranial pain • Temporal artery abnormality • Abnormal temporal artery biopsy • Hunder GG, Bloch DA, Michel BA, et al: The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis, Arthritis Rheum 33:1125, 1990.

6. Giant Cell Arteritis: Pathology • Inflammation in medium-size muscular arteries that originate from the arch of the aorta. • Segmental inflammation with “skip lesions” • Post mortem studies: • greatest frequency of severe involvement in the superficial temporal arteries, vertebral arteries, and ophthalmic and posterior ciliary arteries. • The internal carotid, external carotid, and central retinal arteries were less frequently affected • Proximal and distal aorta , subclavian, brachial, and abdominal arteries. • GCA rarely involves intracranial arteries (intracranial arteries lose elasting lamina after crossing the dura mater

7. Giant Cell Arteritis: Atypical Presentations • Fever of unknown origin (FUO) – 15% • CNS: 30% • TIA or stroke • Peripheral mono or poly-neuropathy • Respiratory: 10% • Cough, sore throat • Aortic aneurism • Pseudotumor

8. Giant Cell Arteritis • Diagnosis: Temporal artery biopsy 90-95% sensitive • Treatment: • High dose corticosteroid • No reliable steroid sparing drugs (MTX) • Biologic therapy: anti-IL6? • Aspirin associated with fewer CVA and less blindness in retrospective analyses

9. PolyarteritisNodosa

10. Small Vessel Vasculitis • ANCA Associated Vasculitis (AAV) • GranulomatousPolyangiitis (GPA) • Microscopic Polyangiitis (MPA) • Cryoglobulinemia • Hepatitis C Associated mixed cryoglobulinemia

11. ANCA Associated Vasculitis • Thrombosis • RAVE study

12. Thrombosis and Vasculitis • Wegener’s GranulomatosisEtancercept Trail (WGET) Research Group. NEJM 2005; 352:351-361 • 16% GPA patients had DVT or PTE • Allenbach Y, Seror R, Pagnoux C et al. Ann Rheum Dis 2009;68: 564-567 • Retrospective study of 1130 patients from French Vasculitis Study Group with GPA, MPA, Churg-Strauss Syndrome (CSS), PAN • DVT: 7.8-8.2 % GPA, MPA, CSS; 2.5% PAN

13. Rituximab versus cyclophosphamide for ANCA-associated vasculitis • Stone  JH,   Merkel  PA,   Spiera  R.  N Engl J Med. 2010 363(3):221-32 • 197 patients • RTX vsCyclophosphamide • Remission without prednisone at 6 months

14. Rituximab versus cyclophosphamide for ANCA-associated vasculitis • Primary end point: remission at 6 months • RTX group: 64% (63/99) • CTX group 53% (52/98) • 11% difference not significant (95.1% confidence interval [CI], −3.2 to 24.3 percentage points; P=0.09) • Non-inferiority (P<0.001) • Secondary end point – <10 mg/d prednisone • RTX : 71% • CTX: 62% • P=0.10

15. Rituximab versus cyclophosphamide for ANCA-associated vasculitis • Adverse effects similar in both groups • Leukopenia: RTX 3%, CTX 10% • Infection: 7% both groups • Hemorhagic cystitis: 1% both groups • Cancer: 1 each group • Death: 1 RTX, 2 CTX • Rituximab + prednisone an alternative to cyclophosphamide + prednisone for induction therapy of ANCA associated vasculitis

16. Cryoglobulinemia • Type I – monoclonal immunoglobulins • B-cell lymphoproliferative disorders • Type II – polyclonal IgG with monoclonal IgG with rheumatoid factor activity • Type III – polyclonal IgG with polyclonal ImG with rheumatoid factor activity • B-cell lymphoproliferative disorder • Autoimmune disease • Infections (HCV)

17. Cryoglobulinemia • Associated laboratory abnormalities • Low C4 serum complement • Monoclonal gammopathy • Rheumatoid factor positivity • Spurious elevation of erythrocyte sedimentation rate (ESR), WBC, platelet count, MCV

18. Cryoglobulinemia • Clinical presentation • Palpable purpura, petechiae • Raynaud’s, acrocyanosis, digital ulcers, gangrene • Peripheral neuropathy • Membranoproliferativeglomerulonephritis

19. Cryoglobulinemia: Rx • HCV mixed cryo: antiviral regimen • Pegylated IFN-alpha • Ribavirin • Rituximab combined with Peg-IFN-α/ribavirin • Blood 2010; 116:325-334 • Rituximab for HCV nonresponders to antiviral • Arthritis Rheum 2012; 64:835-842, 842-853

20. Giant Cell arteritis • Beware of atypical presentatoins • Watch for aortitis • High dose corticosteroid is still standard therapy • Traditional steroid sparing agents disappointing • Anti-IL6 may be emerging therapy • Polyarteritisnodosa • Look for and treat Hepatitis B virus

21. ANCA Associated Vasculitis • Thrombosis is associated with active disease • Rituximab is an alternative to cyclophosphamide for induction therapy • HCV associated mixed cryoglobulinemia: • Rituximab is effective adjunctive Rx in combination with antiviral Rx, and is an alternative to traditional immunosuppressive Rx in antiviral non-responders