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Juvenile idiopathic arthritis associated with autoimmune hepatitis type 2
  1. V Nobili1,
  2. R Devito2,
  3. D Comparcola1,
  4. E Cortis3,
  5. M R Sartorelli1,
  6. M Marcellini1
  1. 1Department of Liver Diseases, Research Institute, Bambino Gesu’ Children’s Hospital, Rome, Italy
  2. 2Department of Pathology, Research Institute, Bambino Gesu’ Children’s Hospital, Rome, Italy
  3. 3Department of Paediatric Rheumatology, Research Institute, Bambino Gesu’ Children’s Hospital, Rome, Italy
  1. Correspondence to:
    Dr V Nobili
    Department of Liver Disease, Research Institute, Bambino Gesu’ Children’s Hospital, Piazza S Onofrio 4, 00165 Rome, Italy;

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Juvenile idiopathic arthritis (JIA) is one of the most common chronic disorders in childhood and affects 1 in 1000 children.1

Recently, the International League of Associations for Rheumatology proposed consensus criteria for the classification of childhood arthritis under the term JIA.2 JIA defines an arthritis developing in patients aged 16 years or younger that has no known cause.

Liver disturbance, although not characteristic of JIA, is common and it has been attributed not only to the liver disease associated with rheumatoid diseases themselves but also to many other factors, such as fatty infiltration, drug toxicity, thrombotic accidents, or autoimmune liver disease.3,4

Autoimmune hepatitis (AIH) is an unresolving inflammation of the liver of unknown cause.5 AIH type 2 (AIH 2) is characterised by the presence of anti-liver kidney microsomal autoantibodies (LKM-1) directed against cytochrome P450IID6.6 Early recognition of the disease and prompt institution of treatment are essential to avoid progression to subacute hepatic failure and the possible need for liver transplantation.

We report an unusual association—namely, a case of severe AIH type 2 in a girl with JIA.


An 8 year old girl was referred to our paediatric rheumatology clinic in June 2003 for assessment of possible JIA because of fever and joint disease affecting the right knee, with synovitis confirmed by ultrasound examination.

At admission she had laboratory evidence of a vigorous response in the acute phase with high erythrocyte sedimentation rate and C reactive protein concentration, neutrophilia, and thrombocytosis. Aminotransferases (alanine aminotransferase (ALT) 123 IU/l, aspartate aminotransferase (AST) 87 IU/l, normal value 5–40 IU/l) were increased, and hypergammaglobulinaemia (27 g/l) and increased serum IgG (18.00 g/l) were detected. The indirect immunofluorescence method showed high titres of circulating antinuclear antibodies (ANA; 1/640) and anti-liver/kidney microsomal antibodies (LKM-1; 1/160), whereas anti-smooth muscle antibodies (ASMA), and antimitochondrial antibodies (AMA) were absent. The child’s HLA haplotype was A2, B8, DR3, DRw52, DQ2, and the family history was unremarkable for autoimmune diseases.

The girl was discharged after 6 days in hospital with a diagnosis of JIA, on oral non-steroidal anti-inflammatory treatment and physiotherapy (to maintain normal joint range and muscle power).

When seen again, 6 weeks later, her clinical improvement continued but aminotransferases (ALT 123 IU/l, AST 87 IU/l) were still increased, and hypergammaglobulinaemia (26 g/l) and increased serum IgG (16.90 g/l) persisted.

Hepatitis A, B, C, D, E, and G, cytomegalovirus, and Epstein-Barr virus infections were ruled out by appropriate tests, which included serum HBV-DNA and HCV-RNA. High titres of ANA (1/640) and anti-LKM-1 antibodies persisted, whereas ASMA and AMA were absent. A percutaneous liver biopsy7 was performed and disclosed hepatitis with bridging necrosis and features consistent with autoimmune hepatitis (portal and periportal lymphoplasmocytic inflammation, active hepatitis at the portal-parenchymal interface, bridging, and spotty necrosis) (fig 1). The diagnosis of AIH type 2 was confirmed and characterised as “definite” by using the scoring system of the International Autoimmune Hepatitis Group.8,9 After treatment with prednisone (2 mg/kg daily) and azathioprine (2 mg/kg daily) AST and ALT concentrations returned to normal in 5 weeks and striking reduction of immunoglobulin levels and IgG (0.96 g/l) were seen.

Figure 1

 Autoimmune hepatitis: portal and periportal lymphoplasmocytic inflammation with hepatitis at the portal-parenchymal interface (active interface hepatitis). Magnification ×20.


The diagnosis of AIH in children with JIA is of paramount importance to guiding treatment and formulating prognosis. Mild abnormalities in liver function tests are common in children with JIA; as few of them undergo liver biopsy, AIH might go undetected.

In conclusion, we believe, in according with Kojima and coworkers10 that liver histology is warranted in differentiating AIH from liver disease associated with rheumatoid disease and must be performed in all children affected by rheumatoid disease associated with persistent alterations in liver function tests.


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