Service de Médecine Interne,
1 Laboratoire de neuropathologie,
2 Laboratoire de virologie,
3 Service de radiologie, Centre Hospitalier Universitaire Pitié-Salpêtrière, 4783 Boulevard de l'Hôpital, 75651 Paris Cedex 13 and
4 Service de Médecine Interne, Centre Hospitalier Général, Rue Gabriel Péri, 77527 Coulommiers Cedex, France
SIR, Numerous extrahepatic manifestations have been associated with hepatitis C virus (HCV), including vasculitis of small vessels, such as mixed cryoglobulinaemia (MC), and diseases of the larger vessels, such as polyarteritis nodosa (PAN) [1]. There is still discussion about whether HCV is responsible for PAN, but the involvement of this virus in MC is well known [24].
We report three patients with HCV infection and systemic vasculitis who presented with numerous visceral microaneurysms. We discuss the problem of the type of systemic vasculitis (PAN or MC) that is present and the therapeutic consequences. In all patients, tests for antineutrophil cytoplasmic antibodies, HBV and HIV infection were negative.
Patient 1 was a 45-yr-old man who was referred in March 1995 for fever, weight loss of 10 kg, peripheral neuropathy, arthralgias, myalgias, abdominal pain, cutaneous purpura and recent onset of hypertension. Biological inflammation was present. A digital abdominal angiogram showed numerous microaneurysms involving the distal branches of both renal arteries, which were associated with renal cortical infarctions (Fig. 1A) and stenosis of the superior mesenteric artery (Fig. 1B
). A neuromuscular biopsy disclosed necrotizing vasculitis involving medium-sized vessels (>100 µm) and small vessels (arterioles and capillaries). The patient was positive for type III cryoglobulinaemia and HCV RNA. The HCV genotype was 3a. Liver biopsy revealed mild chronic hepatitis (Knodell's score 3).
|
|
|
He was treated with the same protocol as patient 1. Clinical and biological remissions were obtained within 2 months. In July 1999, HCV RNA and cryoglobulinaemia were not detectable. Ribavirin and interferon were withdrawn after 1 yr of treatment. In August 2000, the patient was symptom-free and HCV RNA was no longer detectable. Cryoglobulinaemia was 0.02 g/l. Angiography was normal.
Patient 3 was a 45-yr-old woman who was referred in November 1998 for treatment of PAN. Her medical history indicated cutaneous vasculitis that had lasted 20 yr. In 1994, she had had spontaneous rupture of a renal microaneurysm with massive perirenal haemorrhage. She had been treated with corticosteroids for a few months and had shown clinical improvement. In 1995, arterial hypertension was noted. In September 1998, she had a spontaneous hepatic haematoma after the rupture of a macroaneurysm of the right hepatic artery. Embolization of the aneurysm was performed and arteriography showed numerous renal microaneurysms. On admission, she presented with hepatomegaly and biological inflammation. She was positive for HCV RNA and her HCV genotype was 1a. Liver biopsy showed mild fibrosis with chronic hepatitis (Knodell's score 3). Repeated tests for cryoglobulinaemia were negative. She was treated with the protocol described above. Hepatomegaly, inflammatory syndrome and HCV RNA positivity persisted. Digital angiography was unchanged.
We report three patients who presented with severe systemic vasculitis. They all had HCV infection with positive viraemia. Two had mixed cryoglobulinaemia. Treatment was based on the treatment for PAN-related HBV infection proposed by Guillevin et al. [5]. After a few months of maintenance treatment, which included low doses of prednisone, interferon and ribavirin, clinical and angiographic remission was observed in two cases, concomitantly with loss of HCV RNA. This was very similar to the course reported for HBV-related PAN [6].
Numerous and typical microaneurysms in the main visceral arteries were present in all cases, suggesting the involvement of medium-sized arteries [7]. Such radiological lesions, highly suggestive of PAN, may also be seen in necrotizing angiitis associated with drug abuse, Wegener's granulomatosis, systemic lupus erythematosus, thrombotic thrombocytopenic purpura, atrial myxoma and bacterial endocarditis [6] but have never been reported in cryoglobulinaemic vasculitis.
Criteria for the classification of systemic vasculitis are still under debate. They are based on the American College of Rheumatology (ACR) 1990 criteria [8], modified in 1994 by the Chapel Hill Consensus Conference on the nomenclature of systemic vasculitides [7]. All patients fulfilled the ACR criteria for PAN, but according to the Chapel Hill nomenclature the first and second patients, who had involvement of microscopic vessels, could not be classified as having PAN. Instead, according to cryoglobulinaemia positivity, they should be considered as having MC vasculitis. However, these patients presented severe acute clinical manifestations different from those described in HCVMC vasculitis [9, 10]. Thus, three options have to be considered. First, these patients had PAN-type vasculitis and their clinical course provided a strong argument for the existence of PAN related to HCV. Secondly, the patients had MC vasculitis related to HCV, and this is the first report of visceral microaneurysms in this condition. Thirdly, as emphasized by Lie [11], the vasculitides are an extraordinary heterogeneous group of disorders and their classification according to a schema with universal acceptance is virtually an impossible task. According to this view, our patients had unusual forms of HCV-associated vasculitis presenting as classic PAN. This illustrates the great clinical polymorphism of virus-associated vasculitides and the difficulty in classifying the vasculitides.
The treatment and disease course of these patients confirm that when severe systemic vasculitis is the consequence of viral infection, a specific therapeutic scheme with antiviral drugs should be preferred to conventional therapy with steroids and cytotoxic agents.
Notes
Correspondence to: N. Costedoat-Chalumeau.
References