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

Thank youDr John Olerud, Division head; Claudia Davis ARNP, and the Pacific Derm Association