Antiphospholipid antibody syndrome due to interferon
treatment for hepatitis C
Michi Shinohara, MDPacific Dermatologic Association
August 10, 2008
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
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)
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
Autoantibodies and hepatitis C• Development of autoantibodies in setting of
hepatitis C is common - RF– APL Abs including aCL1, LA2 reported in up to
46% of those with hepatitis C
• APS in hepatitis C rare, incidence not increased in setting of hepatitis C1,2
– 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 7:241-2442. Amin, N (2008) Hematol Oncol Clin N Am 22:131-143
Antiphospholipid antibody syndrome and interferon
• Autoantibodies and immune phenomenon common during IFN therapy– Thyroid antibodies in 22%– Appearance or exacerbation of SLE, sarcoidosis1
• 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)
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