Autoimmune Overlap Syndromes

Abstract

The advancement of immunological, molecular biological, and morphological techniques as well as the introduction of diagnostic scoring systems allows for precisely allocating the majority of patients to one of the three major hepatobiliary (auto)immune diseases, i.e. autoimmune hepatitis (AIH), primary biliary cirrho sis (PBC) or primary sclerosing cholangitis (PSC). Up to 20% of these patients, however, share overlapping clinical, histological, and immunological features that do not allow for establishing a precise diagnosis [12]. These patients are said to suffer from a variant or overlap syndrome [10, 23]. The clinician should be aware, though, that this term does not defi ne an exact diagnosis, but rather results from our still unsatisfactory under standing of the precise etiology and pathogenesis of autoimmune liver diseases. The degree of overlap may be minor with signs and symptoms of one disease clearly prevailing, or major with the clinical, serological and histological features of two diseases fully overlapping. In addition to coexistence, two diseases may appear sequentially during follow up. The evolution of one autoimmune liver disease to another does not represent a true overlap, but a sequential syndrome. The knowledge of variant (overlap) syndromes of autoimmune liver disease is not only interesting diagnostically, but also has therapeutic implications. Predominantly cholestatic overlap syndromes are generally more responsive to ursodeoxycholic acid (UDCA) than to immunosuppressive therapy, while hepatitic overlap syndromes respond to immunosuppressive treatment with corticosteroids and azathioprine. If both components, cholestatic and hepatitic, are present in equal measure combination therapy of UDCA and immunosuppressive drugs is warranted. Chapter Outline