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Systemic lupus erythematosus with haemophagocytosis and severe liver disorder
  1. E Maeshima,
  2. T Kobayashi,
  3. M Mune,
  4. S Yukawa
  1. Third Department of Internal Medicine, Wakayama Medical College, 811–1 Kimiidera, Wakayama City, Wakayama 641–0012, Japan
  1. Correspondence to:
    Dr E Maeshima;

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We report the case of a 30 year old woman who was diagnosed with systemic lupus erythematosus (SLE)1 and had received prednisolone and cyclosporin A (CsA). In November 1999 a haematological examination showed a slight increase in transaminases. With no improvement in transaminase values, CsA was discontinued, and prednisolone was continued at 20 mg/day. Because of general malaise, she was admitted in January 2000.


A haematological examination showed a marked decrease in white blood cells (WBC) to 1.4×109/l, with a slight anaemia, but platelets were within the normal range. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were considerably increased to 617 U/l (normal 13–33) and 350 U/l (normal 6–27), respectively. Ferritin was also increased to 2306 ng/ml (normal 5–178). C reactive protein (CRP) was increased to 7.9 mg/l (normal 0–4). Anti-double stranded DNA antibodies were increased to 297.8 IU/ml (normal 0–11.9). CH50 17 U/ml (normal 30–50) showed severe hypocomplementaemia. Soluble interleukin 2 receptor (sIL2R) was high at 807 U/ml (normal 145–519). Serum studies for hepatitis B virus, hepatitis C virus, herpes simplex virus, and Epstein-Barr virus were negative. Direct immunoperoxidase staining using a monoclonal antibody (HRP-C7) measurement, a marker of cytomegalovirus (CMV) antigenaemia, was 1/34 000. This level is associated with asymptomatic CMV antigenaemia.2,3 Bone marrow aspiration and liver biopsy were performed. In the bone marrow, histiocytic haemophagocytosis was seen (fig 1A). Liver biopsy showed moderate centrilobular large droplet fatty degeneration, hepatocytic rupture-induced lipogranuloma, and focal necrosis of hepatic cells (fig 1B). There was no lymphocyte invasion or intracytoplasmic inclusion bodies. Immunostaining was negative for CMV. Reactivated SLE associated with haemophagocytosis and a liver disorder was diagnosed. Gammaglobulin and ganciclovir were given for CMV antigenaemia. The CRP declined and CMV became negative, but fever continued. WBC decreased to 1.1×109/l, and AST and ALT further increased to 1081 U/l and 591 U/l, respectively, with a remarkable reduction in the CH50 to 9 U/ml.

Figure 1

(A) Haemophagocytosis in bone marrow. The histiocyte showed phagocytosis of various haemopoietic cells including granulocytes, platelets, and erythrocytes. (May-Giemsa stain, original magnification ×1000.) (B) The findings of hepatocytes rupture-induced lipogranuloma with focal necrosis of hepatic cells. (Haematoxylin-eosin stain, ×200.)

Betamethasone was given at 6 mg/day, and CsA was resumed at 200 mg/day. Subsequently, fever abated, and the WBC increased to 3.4×109/l and eventually reached normal. sIL2R fell to normal. Transaminases gradually improved, and she was discharged in April 2000. Finally, transaminases fell to the normal range in June 2000.


Possible causes of haemophagocytosis include viral infections in this patient, as well as SLE itself, because the disease was active. However, owing to the negative results of serum studies for several viruses, SLE itself was thought to be the cause of haemophagocytosis.

sIL2R, a marker of activated T cells,4 increases in active SLE or rises before activation of SLE.5–7 It is evident from these reports that activated T cells play an important part in the pathophysiology of active SLE. Both immune complex and hypocomplementaemia and also activated T cells played an important part in the mechanism of haemophagocytosis in our patient. CsA, which inhibits helper T cells,8 was effective, suggesting that cytokines also were important in the mechanism of haemophagocytosis.

In SLE, greatly increased transaminases are uncommon. In our patient, according to the definition and diagnostic criteria for CMV infection-induced hepatitis and cholangitis,9 CMV hepatitis was unlikely. Infections due to viruses other than CMV were also unlikely because no inclusion body was found. In addition, an examination of her liver did not point to a hepatic disorder induced by a thrombotic event. Steatosis found in SLE is generally accepted as a condition associated with drugs such as corticosteroids.10 However, hepatic disorder in our patient occurred as part of active SLE, and activated T lymphocytes and hypercytokinaemia played important roles as in the mechanism of haemophagocytosis, because sIL2R was high and improved as the clinical symptoms and liver transaminases improved with combined treatment with corticosteroids and CsA.


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