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Giant cell arteritis of the leg in a patient with hepatitis C virus infection
  1. CLAUDIO VITALI,
  2. EDI GALLUZZO
  1. Rheumatology/Clinical Immunology Units of the University of Pisa, Italy
  2. Histopathology Unit of S Chiara Hospital of Pisa, Italy
  3. Blood Centre of S Chiara Hospital of Pisa, Italy
  4. Gastroenterology Unit of the University of Pisa, Pisa, Italy
  1. Dr C Vitali, Rheumatology and Clinical Immunology Units, University of Pisa, via Roma 67, 56126 Pisa, Italy.
  1. EUGENIO M CIANCIA
  1. Rheumatology/Clinical Immunology Units of the University of Pisa, Italy
  2. Histopathology Unit of S Chiara Hospital of Pisa, Italy
  3. Blood Centre of S Chiara Hospital of Pisa, Italy
  4. Gastroenterology Unit of the University of Pisa, Pisa, Italy
  1. Dr C Vitali, Rheumatology and Clinical Immunology Units, University of Pisa, via Roma 67, 56126 Pisa, Italy.
  1. ADOLFO MORETTI
  1. Rheumatology/Clinical Immunology Units of the University of Pisa, Italy
  2. Histopathology Unit of S Chiara Hospital of Pisa, Italy
  3. Blood Centre of S Chiara Hospital of Pisa, Italy
  4. Gastroenterology Unit of the University of Pisa, Pisa, Italy
  1. Dr C Vitali, Rheumatology and Clinical Immunology Units, University of Pisa, via Roma 67, 56126 Pisa, Italy.
  1. SANTINO MARCHI
  1. Rheumatology/Clinical Immunology Units of the University of Pisa, Italy
  2. Histopathology Unit of S Chiara Hospital of Pisa, Italy
  3. Blood Centre of S Chiara Hospital of Pisa, Italy
  4. Gastroenterology Unit of the University of Pisa, Pisa, Italy
  1. Dr C Vitali, Rheumatology and Clinical Immunology Units, University of Pisa, via Roma 67, 56126 Pisa, Italy.

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The potential association of chronic hepatitis C virus (HCV) infection with a variety of dermatological features has been reported.1 In particular, it has been observed that different types of cutaneous vasculitis may develop during the course of HCV infection,1-5 such as mixed cryoglobulinaemia related leucocytoclastic vasculitis and polyarteritis nodosa.

We report a case of giant cell arteritis (GCA) involving the medium sized dermal arteries of the right leg, which appeared after a long history of HCV infection.

A 44 year old man with an eight year history of chronic hepatitis was admitted to the Rheumatology/Clinical Immunology Units of the University of Pisa in July 1995 because of erythematous cutaneous nodules on the legs. Chronic hepatitis had been suspected since 1987 because of raised, fluctuating values of hepatic enzymes. In 1993 the diagnosis was confirmed by liver biopsy. In June 1995 the presence of anti-HCV antibodies was demonstrated by an ELISA test. From the time of the histopathological assessment of chronic hepatitis to that of the appearence of the cutaneous nodules the patient was not receiving any medical treatment.

At the time of his stay in hospital the patient underwent a complete physical examination, which showed no abnormalities except for the cutaneous lesions. These were tender, red, and painful nodules situated on the medial side of the right leg, which appeared to be confluent in some areas.

Routine laboratory investigation showed only a moderate increase of the acute phase reactants (erythrocyte sedimentation rate 29 mm 1st h, C reactive protein 2.9 mg/dl, fibrinogen 600 mg/dl).

Antineutrophil cytoplasmatic antibodies (ANCA), antinuclear antibodies, immune complexes, and cryoglobulins were absent. Hepatitis B virus markers (antibodies to hepatitis B, anti-HBc, and anti-HBe, and the HBs and HBe antigens) were not detected in the serum, nor were the antibodies anti-HIV1 and -HIV2.

On the contrary, anti-HCV antibodies were found using a third generation ELISA test (Abbott HCV EIA 3.0, Abbott Diagnostics, Wiesbaden-Dielkenhein, Germany). A qualitative ‘dot’ assay (Abbott HCV MATRIX, Abbott Diagnostics, Wiesbaden-Dielkenhein, Germany) showed that these antibodies were directed to the HC-34 core and HC-29 NS3 recombinant proteins, while there was no serological reactivity against the c-100-3 NS4, HC-23 NS4 viral recombinant antigens.

The presence of viral RNA (indicative of active HCV replication) in the serum was demonstrated by a polymerase chain reaction (PCR Primer 5’ UTR, Roche Diagnostic Systems, Branchburg, NJ, USA). The viral genotype was 2a (Inno-LiPA HCV, Nuclear Laser Medicine, Milan, Italy). Liver biopsy showed a mild, chronic hepatitis that was classified as grade 2, stage 2 according to a recently proposed scoring system.6A skin biopsy specimen taken from a nodular lesion on the right leg showed inflammation and thrombosis of a medium sized dermal artery with presence of a number of Langhans type multinucleate giant cells (fig 1). An immunohistochemical procedure, using an anti-CD68/KP1 monoclonal antibody (DAKO, Glostrup, Denmark) showed a specific staining of the multinucleate giant cells, this confirming that those cells were monocytic/macrophagic elements in origin. On the whole, this picture could be considered suggestive of a giant cells arteritis. An angiogram of the coeliac axis and the superior mesenteric artery did not show any aneurysmal dilatations in the small and medium sized arteries suggestive of polyarteritis nodosa. A clinical examination was completed that excluded any other infectious, immuno-mediated or neoplastic disorders, which could potentially be linked to the presence of granulomatous lesions of the medium sized arteries.7

Figure 1

(A) Medium sized artery with acute and chronic transmural inflammation without signs of extension of the process to the surrounding tissue. The lumen is partially obstructed by a thrombus (magnification × 40, haematoxilin and eosin stain). (B) A typical Langhans-type giant cell can be clearly seen in the upper left corner. Other giant cells are barely discernible along the lower edge. The infiltrate is mainly constituted of granulocytes and mononuclear cells. Eosinophils are present in very limited amounts (no more than 2% of the infiltrating cells) (magnification × 200, haematoxilin and eosin stain).

Corticosteroid therapy (6-methyl-prednisolone 16 mg per day) was started and was progessively tapered to a low dose maintenance regimen of 4 mg. The cutaneous lesions completely disappeared within four weeks after beginning this treatment.

In the patient described here GCA developed in limited areas in the skin of the right leg during the course of a chronic HCV infection. The persistence of HCV infection was demonstrated by the presence of anti-HCV antibodies, and of viral RNA in the serum whose genotype was compatible with the mild form of chronic hepatitis that had been reported by the liver histopathology.8 The diagnosis of GCA was confirmed by histopathological and immunohistochemical studies, which showed an inflammatory infiltrate in the walls of the medium sized arteries composed of numerous mononuclear cells and scattered Langhans-type giant cells. To our knowledge, this association has never been reported before in the medical literature.

Multi-nucleated giant cells are a common feature of the granulomas that may develop during various inflammatory reactions. These elements originate from the fusion of monocytes or macrophages,9with the cooperation of adhesion molecules.10 Giant cell granulomas are the characteristic feature of the granulomatous vasculitides, including Wegeners granulomatosis.11However, giant cell granulomas are the histopathological hallmark of two clinical entities, Takayasu’s arteritis and Horton’s arteritis. In the first the aorta and its branches (including the proximal coronary and renal arteries) are generally involved; in the second the temporal artery is classically affected and, more rarely, the other extracranial or intracranial branches of the carotid.12

The typically sudden onset of GCA, accompanied by fever and other generalised complaints, has raised the possibility that the disorder may be triggered by an infection although a convincing experimental support is lacking.13 However, a retrospective epidemiological study has shown that Horton’s arteritis exhibits a regular, cyclic pattern of incidence, thus indirectly supporting the hypothesis of an infectious cause.14

It is known that different vasculitides may occur in HCV infected patients. Leucocytoclastic small vessel vasculitis has been widely reported in patients with chronic HCV infection and circulating mixed cryoglobulins.2 3 At the same time, conflicting data exist on the possible association between HCV infection and panarteritis nodosa.4 5

This case adds yet another to the list of the different vasculitides that may be associated with HCV infection, and in addition provides support for the interesting, but as yet unproved hypothesis that granulomatous vasculitides of the medium sized vessels, including giant cell arteritis, may be an antigen driven process, possibly triggered by an infectious agent.15

References

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