1 I. Medizinische Klinik und Poliklinik, and 2 Institut für Pathologie, Johannes Gutenberg-Universität Mainz, Germany
Correspondence and offprint requests to: Dr Eveline Wandel, I. Medizinische Klinik und Poliklinik, Johannes Gutenberg-Universität Mainz, Langenbeckstr. 1, D-55101 Mainz, Germany.
Keywords: acanthocytes; cryoglobulins; glomerolonephritis; hepatitis C virus; haematuria; interstitial vasculitis; subendothelial deposits
Case report
A 58-year-old woman was referred to the dermatology department with a vasculitic rash confined to the calfs and ankles. Over the last 6 years she had had a similar rash in the same area particularly during the winter. Because of a psychiatric illness she was on treatment with haloperidol. Seven years before admission she had had a hysterectomy; because of post-operative haemorrhage she had received several units of blood. Upon questioning she complained about occasional arthralgia in the hands and wrists. Small and confluent purpuric lesions were noted on calfs and ankles and spotty hyperpigmentation was also present. Small ulcers were seen on the lateral aspect of the ankles.
A blood count was normal apart from mild thrombocythaemia, i.e. 465/nl (normal 120350/nl). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and bilirubin were normal. Gamma-glutamyl transferase was slightly elevated (22 U/l; normal <20 U/l). There was an elevation of the C-reactive protein (1.6 mg/dl; normal <0.5 mg/dl) and fibrinogen (666 mg/dl; normal 150350 mg/dl). Electrolytes were normal as was the kidney function with a creatinine of 0.87 mg/dl (normal <0.9 mg/dl). The total serum protein was decreased (58.0 g/l) with normal albumin, an increased alpha-2 globulin fraction (14.2%) and markedly decreased IgA (0.57 g/l; normal 0.94.5 g/l) and IgG (3.9 g/l; normal 818 g/l). IgM was normal. Immune-electrophoresis showed a monoclonal IgM band. Rheumatoid factor was positive with 46 U/ml (normal <38 U/ml). Proteinuria was 2.6 g/24 h (mainly albumin). Microscopic urine analysis showed haematuria of glomerular origin (727 erythrocytes/ml including 8.4% acanthocytes and the typical stary sky pattern, indicating renal vasculitis (Figure 1).
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Serology was negative for hepatitis B virus and positive for hepatitis A virus (IgG). Hepatitis C virus serology was positive, active hepatitis C virus (HCV) infection was confirmed by detection of HCV-RNA using polymerase chain reaction.
A liver biopsy specimen showed chronic active hepatitis C (Figure 2). Kidney biopsy showed cryoglobulinaemic glomerulonephritis with mild mesangial proliferation (Figures 3 and 4
). Interstitial infiltration with lymphocytes and occasional neutrophils was noted as well as modest interstitial fibrosis. Electron microscopy showed subendothelial organized glomerular deposits. The diagnosis was HCV induced type II mixed cryoglobulinaemia and cryoglubulinaemic glomerulonephritis (membranoproliferative GN).
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In more than 50% of patients chronic hepatitis C infection is accompanied by mixed cryoglobulinaemia (MC) [1]. Membranoproliferative glomerulonephritis with subendothelial deposits (cryoglobulinaemic glomerulonephritis) develops almost exclusively in subjects with type II cryoglobulinaemia, which is characterized by polyclonal IgG and a monoclonal IgM with rheumatoid factor activity [2].
Before identification of the hepatitis C virus as principal causative agent of this disease the majority of cases were treated with corticosteroids and/or cyclophosphamide [2]. Two randomized controlled studies [3,4] have reported limited improvement of renal parameters when treating patients with HCV associated type II MC with alpha-interferon, but most patients relapsed when the treatment was stopped.
The present case illustrates the value of urinary phase-contrast microscopy to monitor the activity of glomerulonephritis lesions [5,6].
Teaching Point
Acknowledgments
The authors thank Mrs Pavisa for excellent technical assistance in performing the phase-contrast-microscopy of the urine.
References