1. Antiphospholipid antibody syndrome due to interferon  treatment for hepatitis C Michi Shinohara, MD Pacific Dermatologic Association August 10, 2008

2. Case presentation 53 yo woman with 3 week history of progressive superficial cutaneous thrombosis History of Hep C with cryoglobulinemia and cutaneous vasculitis, s/p IFN  and ribavarin IVDU > 10y ago, current skin lesions in areas of prior injection Health otherwise stable, no dyspnea, chest pain or leg edema

5. Work up Upper extremity duplex confirmed superficial clot; no DVT Assessed for hypercoaguable state –Anticardiolipin antibodies, lupus anticoagulant, inherited thrombophilias, cryoglobulins negative –  2 glycoprotein-1 Ab (  2-GP-1) titer >99th percentile Referred to hematology, initiated on anticoagulation for antiphospholipid antibody syndrome (APS)

6. Antiphospholipid antibody syndrome Primary or secondary (SLE) Diagnosis based on antiphospholipid antibodies “aPL Abs” (LA, aCL,  2-GP-1) and clinical features (thrombosis, fetal loss) Pathogenesis due to aPL Ab binding to phospholipid associated proteins, especially  2-GP-1 –Main antigenic target of aPL Abs –Clotting inhibitor required for binding of aCL with cardiolipin

7. Autoantibodies and hepatitis C Development of autoantibodies in setting of hepatitis C is common - RF –APL Abs including aCL 1, LA 2 reported in up to 46% of those with hepatitis C APS in hepatitis C rare, incidence not increased in setting of hepatitis C 1,2 –aPL Abs due to infection “cofactor independent”, nonthrombogenic –No increased incidence of  2-GP-1 antibodies 1.Ordi-Ros et al, (2000) Clin and Diag Lab Immuno 7:241-244 2.Amin, N (2008) Hematol Oncol Clin N Am 22:131-143

8. Antiphospholipid antibody syndrome and interferon Autoantibodies and immune phenomenon common during IFN therapy –Thyroid antibodies in 22% –Appearance or exacerbation of SLE, sarcoidosis 1 Our patient had mildly elevated  2-GP-1 antibodies prior to therapy (22 SGU, ref range 0-9) which rose markedly after IFN Also developed sarcoidosis in tattoo 1. Hauschild et al (2008) J Deutschem Dermatol ISSN: 1610-0387 (Online)

10. Conclusions Numerous autoimmune phenomena attributable to hepatitis C as well as immunomodulatory treatment Although development of APS is rare, consider screening for aPL Abs in patients with thrombosis in setting of hepatitis C or interferon treatment

11. Thank you Dr John Olerud, Division head; Claudia Davis ARNP, and the Pacific Derm Association