PBC-AIH overlap syndrome with concomitant ITP and Hashimoto?s disease with positivity for anti-centromere antibody

Abstract

We report a case of primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome with concurrent idiopathic thrombocytopenic purpura (ITP) and Hashimoto's disease with positivity for anticentromere antibody. The patient was a 64-year-old woman with symptoms of jaundice and general fatigue. About 30 years earlier, she had been diagnosed as having ITP and had undergone splenectomy. As part of her present history, she had exhibited liver dysfunction in 1995, during the follow-up of Hashimoto's disease, and a liver biopsy led to the diagnosis of PBC. In March 2000, she was admitted to hospital because of general fatigue and jaundice. Blood tests revealed: total protein (TP), 6.6 g/dl; gamma-globulin (glb), 35.9%; total bilirubin (T-bil), 9.41 mg/dl; direct bilirubin (D-bil), 7.52 mg/dl; aspartate aminotransferase (AST), 957 U/l; alanine aminotransferase (ALT), 651 U/l; alkaline phosphatase (ALP), 595 U/l; gamma-guanosine triphosphate (GTP), 129 U/l; IgG, 2620 mg/dl; IgM, 223 mg/dl; hepatitis B surface antigen (HBsAg), negative; anti-hepatitis C virus (HCV), negative; antinuclear antibody, positive; antimitchondrial antibody (AMA), negative (by the immunofluorescence [IF] method); and anti-pyruvate dehydrogenase complex (PDC)-E2 antibody, positive (by Western blotting). Anticentromere antibody (ACA), which is an alternative diagnostic marker for PBC, was detected in this patient. Prednisolone was administered after admission and liver function test results improved markedly. The liver biopsy in 1995 had revealed infiltration of lymphocytes and plasma cells in the portal areas with fibrous expansion and periportal necrosis. Destructive cholangitis was observed, as well as scattered epitheloid cell granulomas in some portal areas. Liver biopsy after the steroid treatment revealed alleviated necrotic inflammatory responses of hepatocytes, while the destructive cholangitis persisted. This is a very rare case of PBC-AIH overlap syndrome accompanied by ITP and Hashimoto's disease which provides a possible insight into the mechanisms and interplay of autoimmune diseases.

The pathophysiology of thrombocytopenia in chronic liver disease

“… 66 Up to 40% of patients with PBC have raised levels of PAIgG, 66 and there are case reports of patients with autoimmune-related liver disease with ITP. 67 …”

Autoimmune Hepatitis with Concomitant Idiopathic Thrombocytopenic Purpura Diagnosed by Transjugular Liver Biopsy

“…The presence of autoimmune diseases other than ITP should be noted on clinical practice. Although not admitted in this case, there are numerous previous reports of AIH complicated with other autoimmune diseases in addition to ITP, such as primary biliary cholangitis, Sjögren's syndrome, and chronic thyroiditis [2, 8–12].…”

“…In contrast, ITP is caused by immune system dysregulation and the development of autoantibodies for platelet surface glycoproteins (GP) including GPIIb-IIIa, GPIb-IX, and GPIa-II [3, 4]. The prevalence of ITP among patients with AIH in Japan is reported to be 0.6% [2], and there are numerous previous case reports of AIH associated with ITP [5–12]. Although the frequency of autoantibodies against platelet surface GP in patients with AIH remains poorly understood [7–9], some previous reports described that HLA class II genes, which are associated with susceptibility to AIH, influence the production of anti-GP antibody specificities, suggesting a relationship between AIH and ITP [13, 14].…”

Overlap syndromes: An emerging diagnostic and therapeutic challenge

“…There are various reports of PBC–AIH overlap presenting with other autoimmune manifestations like concurrent Idiopathic Thrombocytopenic Purpura ITP and systemic sclerosis,[ 69 ] antiphospholipid syndrome,[ 70 ] concomitant ITP and Hashimoto's disease,[ 71 ] autoimmune hemolytic anemia,[ 72 ] and membranous glomerulonephritis,[ 73 ] which suggest the presence of shared genetic susceptibility factors in multiple autoimmune conditions.…”