Department of Gastroenterology and 1 Department of Pathology, Toranomon Hospital, Tokyo, Japan
Correspondence to: M. Hinata, Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo 105-0001, Japan. E-mail: mhinata{at}hotmail.com
SIR, WeberChristian disease (WCD) is an unusual idiopathic disorder characterized by non-suppurative nodular panniculitis with fever and cutaneous lesions [1]. The aetiology of WCD remains unknown, and systemic WCD, associated with severe liver damage, is often fatal [2]. Hepatic injury associated with WCD is characterized by steatohepatitis [3, 4]. To our knowledge, however, WCD with biliary ductopenia has not yet been reported. We report the first case of systemic WCD with biliary ductopenia that was successfully treated with cyclosporin A (CyA).
The patient was a 27-yr-old Japanese man with recurrent episodes of subcutaneous nodules on both legs since 1995. In January 1998 he was admitted to the Department of Dermatology at our hospital because of a middle-grade fever, bilateral pitting oedema and subcutaneous nodules. Laboratory tests showed the following results. A complete blood count revealed a leucocyte count of 2.3 x 103/µl (89% band cells, 6% lymphocytes, 2% monocytes). Haemoglobin level was 10.7 g/dl and haematocrit 33.5%. Platelet count and coagulation tests were normal. The patient was found to have severe malnutrition with extremely low serum concentrations of total protein and albumin (5.8 and 2.3 g/dl, respectively). The serum concentrations of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase, -glutamyl transpeptidase and creatine kinase were elevated to 173, 74, 1506, 745, 113 and 199 IU/l, respectively. The serum concentrations of total bilirubin (T-Bil), pancreatic enzymes and
1-antitrypsin were within the normal range. Serum ferritin level was markedly increased (34 783 ng/dl). ANA was positive, while the other antibodies and microbiological tests were negative. A small amount of bilateral pleural effusion, moderate fatty liver, a moderate amount of ascites and diffuse intestinal oedema were detected by abdominal ultrasonography or CT. Bone marrow aspirate showed no histiocytic infiltration. A skin biopsy showed panniculitis, which included infiltration of lymphoid cells and granulomatous inflammation of epithelioid cells. He was diagnosed with WCD and treated unsuccessfully with pulse steroid therapy (intravenous methylprednisolone, 1 g/day for 3 days). He was transferred to our department because of his worsening clinical condition and laboratory tests (Fig. 1A). Gastrointestinal bleeding associated with disseminated intravascular coagulation (DIC) and severe jaundice were observed. T-Bil and soluble interleukin-2 receptor (sIL-2R) concentrations were extremely high at 23.5 mg/dl and 13 500 U/ml, respectively. In February 1998, the patient was treated with intravenous CyA and plasma exchange therapy, achieving a plasma CyA concentration of 100 ng/ml. Three weeks later oral CyA therapy (225 mg/day) was started instead of intravenous CyA infusion because of almost complete recovery. Before steroid therapy, a liver biopsy showed periportal steatosis with granulomatous changes and reduction of bile ducts, biliary ductopenia, infiltration of inflammatory cells and severe fatty changes around the portal vein area (Fig. 1B). However, CyA therapy significantly improved the liver histopathology (Fig. 1C), with reduction of inflammatory cell infiltration and periportal steatohepatitis, and regeneration of small bile ducts. Based on this improvement, CyA and corticosteroid treatment was discontinued in 1999. He has been symptom-free and has maintained a normal life style for more than 5 yr without CyA and steroids.
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In addition, a striking feature of this case was the hepatic involvement. Liver biopsy before steroid pulse therapy showed periportal steatohepatitis with biliary ductopenia. Ductopenia is a rare cause of prolonged, progressive cholestatic liver disease [10]. It is mainly associated with chronic allograft rejection, graft-versus-host disease, primary biliary cirrhosis, drugs and toxins. Ductopenia associated with WCD is rare and our report is the first to describe ductopenia as one of the pathological features of WCD and to show that CyA is significantly effective in ductopenia associated with steroid-resistant WCD.
In conclusion, we report a case of WCD with biliary ductopenia successfully treated with CyA. Ductopenia should be included as a possible pathophysiological factor of hepatic lesion in WCD.
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The authors have declared no conflicts of interest.
References
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