Virus-related Polyarteritis Nodosa Research Articles

Classic polyarteritis nodosa associated with hepatitis C virus infection: a case report

IntroductionHepatitis C virus has been under-recognized as an etiologic factor for polyarteritis nodosa and the presence of hepatitis C antigenemia in patients with polyarteritis nodosa has been reported as insignificant. In the literature hepatitis C virus-associated polyarteritis nodosa is a rare and controversial entity.Case presentationA 34-year-old Sri Lankan Tamil man presented to our facility with a two-week history of slow-resolving pneumonia of the right mid and lower zones. On physical examination he had panniculitic type tender skin nodules with background livedo reticularis. A skin biopsy was suggestive of a small and medium vessel vasculitis compatible with polyarteritis nodosa. He was tested positive for hepatitis C antibodies. A serum cryoglobulin test was negative but perinuclear antineutrophilic cytoplasmic antibody test was positive. Serum complement levels were reduced. He was diagnosed as having classic polyarteritis nodosa associated with hepatitis C infection. He later developed left-sided radiculopathy involving both upper and lower limbs and an ischemic cardiac event. His hepatitis C infection was managed with polyethylene glycol-interferon 2α combined with oral ribavirin. Simultaneously, his classic polyarteritis nodosa was treated with prednisolone and cyclophosphamide. He made a good recovery.ConclusionsHepatitis C virus infection is capable of inducing a fulminant form of vasculitis in the form of polyarteritis nodosa. It may be easily confused early in its course with mixed cryoglobulinemia, which is commonly known to be associated with hepatitis C virus. Awareness of hepatitis C virus-related polyarteritis nodosa helps in diagnosing the condition early so combined immunosuppressive and antiviral treatment can be started as soon as possible.

Virus-Associated Vasculitides

Several viruses have been suspected of causing or triggering vasculitis, with hepatitis B virus-related polyarteritis nodosa (HBV-PAN) and hepatitis C virus-related mixed cryoglobulinemic vasculitis (HCV-MCV) having the best demonstrated and confident proof for a causal link with viruses. Human immunodeficiency virus, erythrovirus B19, cytomegalovirus, varicella-zoster virus or human T-cell lymphotropic virus-1 can also induce mainly localized vasculitis. Conversely, no strong evidence indicates that viruses are implicated in the pathogenesis of other primary systemic vasculitides, like Kawasaki or Behcets diseases, or granulomatosis with polyangiitis (Wegeners). Treatment for all these virus-associated vasculitides should be two-pronged: one to control and clear the viral infection, using antiviral drugs; the other to rapidly control the clinical manifestations of vasculitis. Management of this second concomitant therapy is more delicate. It can rely on plasma exchange to clear immune complexes in HBV-PAN or rituximab in HCV-MCV, but sometimes it must include short durations of corticosteroids, and cytotoxic agents for most severe cases, both of which are potentially deleterious because they can hamper virus clearance and delay seroconversion. Keywords: Vasculitis, HBV-related polyarteritis nodosa, HCV-associated cryoglobulinemic vasculitis, HIV infection, Behcet's diseases, leukocytoclastic vasculitis, vasculopathy, Retinitis, Erythrovirus B19, systemic vasculitis

Hepatitis B Virus-Related Polyarteritis Nodosa Presenting With Multiple Lung Nodules and Cavitary Lesions

The patient presented here is a 59-year-old Japanese man with active chronic hepatitis B with precore and core promoter mutated virus, presenting with high fever, bloody sputum, and multiple lung nodules with excavation. Surgical biopsy of the lung nodule showed necrotizing vasculitis affecting pulmonary arteries without granulomatous changes. The pulmonary manifestations of this patient resembled Wegener granulomatosis. However, the pathologic findings showing nongranulomatous necrotizing vasculitis involving the small pulmonary arteries, presence of circulating immune complex, absence of antineutrophil cytoplasmic antibodies, and excellent response to the combination therapy of corticosteroid and an anti-hepatitis B virus agent, entecavir, led us to the diagnosis of hepatitis B virus-related polyarteritis nodosa (PAN). Radiographic evidence of lung nodules or cavitations seen in systemic vasculitis patients has been considered a sign suggestive of granulomatous disease and a diagnostic surrogate marker for necrotizing granulomatous vasculitis, but a clinical relevance to hepatitis B virus-related PAN has not been reported before this case.

Indications for biotherapy in systemic vasculitides

Biotherapy now holds a specific place in the therapeutic armamentarium for systemic vasculitides. Such therapy includes cytokines, such as (pegylated) alpha-interferon for hepatitis B virus-related polyarteritis nodosa and hepatitis C virus-related cryoglobulinemic vasculitis, and polyvalent immunoglobulin (IVIg), with well-defined indications and pending positive results. More specifically targeted monoclonal antibodies include antitumor necrosis factor-alpha or anti-CD20 for antineutrophil cytoplasmic antibody-associated vasculitides or anti-interleukin-5 and anti-IgE for Churg-Strauss syndrome. However, the exact indications of these latter new agents, as well as their optimal dosage and duration, are not defined. Therefore, they are prescribed mainly for patients with disease refractory to conventional therapy, in whom results are promising. Results of international ongoing trials will determine whether the agents may also have a place as first-line treatment.

Hypertensive crisis, hepatitis B virus and polyarteritis nodosa in a child

We report on a case of hepatitis B virus-related polyarteritis nodosa (PAN) in a 4-year-old Turkish boy who was first admitted because of severe arterial hypertension. The diagnosis of PAN was provided by conventional renal arteriography and the child was successfully treated with intensive sequential therapy combining short-term prednisone, plasma exchange and interferon-alpha-2b. Nine years later, he had no sign of PAN, normal blood pressure and normal renal function in the absence of any treatment.

Treatment of hepatitis B virus-related polyarteritis nodosa: two case reports and a review of the literature

A substantial number of cases of polyarteritis nodosa (PAN) are related to hepatitis B virus (HBV) infection. Different treatment strategies are reported in the literature. The aim of this study was to review 15 years of literature (1988-2002) to determine the optimal treatment for HBV-related PAN at present, and to discuss the indications and mechanism of action of corticosteroids in HBV-related PAN, as many physicians are reluctant to use these in the presence of HBV infection. The first patient stopped his initial treatment, relapsed and died of cerebral infarction. The second case illustrates the favorable outcome with the standard treatment: corticosteroids, lamivudine and plasma exchanges. If adequate follow-up is possible, antiviral agents as well as corticosteroids are indicated in HBV-related PAN. Corticosteroids diminish inflammation and corticosteroid withdrawal induces an alanine aminotransferase (ALT) rebound in patients with a low baseline ALT level. Antiviral agents are essential, as they reduce the production of HBV antigens and help to achieve hepatitis B early antigen (HBeAg) seroconversion. Plasma exchanges reduce the level of circulating immune complexes and are included in the treatment protocol of all recent studies. However, their effect has not been evaluated in controlled trials. We concluded that if adequate follow-up is possible, antiviral agents as well as corticosteroids are indicated in HBV-related PAN.

Temporal artery biopsy: a diagnostic tool for systemic necrotizing vasculitis. French Vasculitis Study Group.

To describe the clinical, biologic, and histologic features of temporal artery biopsy (TAB)-localized systemic necrotizing vasculitides (SNV), and to assess their frequency among elderly patients undergoing TAB for suspected giant cell (temporal) arteritis (GCA). The frequency of a TAB localization of SNV was prospectively assessed in a multicenter study of elderly patients undergoing TAB for suspected GCA. All patients with SNV fulfilling the American College of Rheumatology criteria for a specific vasculitic syndrome and with evidence of vasculitis on TAB were included in a retrospective, descriptive study. SNV was diagnosed based on the TAB in 1.4% of the patients with suspected GCA and in 4.5% of the positive (inflamed) TAB specimens. We retrospectively selected 27 patients (18 female, 9 male; mean +/- SD age 62+/-15 years, range 22-79 years) with SNV and TAB-localized vasculitis. Only 2 of these patients were known to have SNV before TAB localization. Twenty-two patients (81%) had cephalic symptoms, including jaw claudication in 33%, clinically abnormal temporal arteries in 33%, and neuro-ophthalmologic symptoms in 11%. All patients had systemic symptoms suggestive of SNV and histologically proven NV in the TAB specimens (70%) or elsewhere in other biopsy sites (74%). Abnormal biologic results suggestive of SNV were present in 17 patients (63%). For 4 patients, the TAB-documented involvement led to initial misdiagnoses of GCA, and systemic manifestations that developed under steroid therapy revealed the correct diagnosis. The final diagnoses of the patients were polyarteritis nodosa (PAN) (n = 11), Churg-Strauss syndrome (n = 6), micropoly-angiitis (n = 3), Wegener's granulomatosis (n = 3), hepatitis B virus-related PAN (n = 2), hepatitis C virus-related cryoglobulinemic vasculitis (n = 1), and rheumatoid vasculitis (n = 1). TAB-localized SNV presents a major diagnostic dilemma because it can mimic GCA. Careful analysis of clinical, biologic, and histologic data should lead to the correct diagnosis and help guide the clinician's choice of appropriate therapy.

The spectrum and treatment of virus-associated vasculitides.

It is admitted that viral infections can be responsible for systemic vasculitides. Viruses can be responsible for various types of vasculitis that affect vessels of different sizes. Clinical manifestations are the same as those observed in previously described vasculitides such as polyarteritis nodosa or cryoglobulinemia. When viral infection is diagnosed and considered to be responsible for vasculitis, a specific therapeutic approach must be prescribed. Treatment is based on the combination of antiviral agents and symptomatic or immunomodulating therapies. Antiviral therapy facilitates virus clearance and seroconversion to specific antibodies. In systemic vasculitides, plasma exchanges are a powerful treatment that clears circulating immune complexes. In the case of digital ischemia, vasodilators are also useful. Conversely, steroids and cytotoxic agents stimulate virus replication and favor disease chronicity and deleterious effects due to the presence of the virus. Hepatitis B virus-related polyarteritis nodosa can be cured with the combination of antiviral agents (mainly interferon alpha) and plasma exchanges. Hepatitis C virus-related cryoglobulinemia responds to interferon alpha and sometimes to plasma exchanges, but responses are usually partial and relapses occur in the majority of cases. In HIV-related vasculitides, currently available antiretroviral agents are not able to definitively eradicate the virus but their combination with plasma exchanges can cure the vasculitis. Due to common epidemiologic factors, several viruses can be present in the same patient, and determining their responsibility in the vasculitic process requires careful clinical and virologic analysis and then the selection of a specifically adapted therapeutic regimen. The therapeutic strategy applied in virus-associated vasculitides is therefore based on the etiologic investigations and the choice of a treatment is adapted to the pathogenetic mechanisms.

Prognostic Factors in Polyarteritis Nodosa and Churg-Strauss Syndrome A Prospective Study in 342 Patients

We undertook this study to determine the clinical, biologic, immunologic, and therapeutic factors associated with the prognoses of polyarteritis nodosa (PAN) and Churg-Strauss syndrome (CSS). Three hundred forty-two patients (260 with PAN, 82 with CSS) followed from 1980 to 1993 were included in a prospective study on prognostic factors. Two hundred eighty-eight of these patients were included in the prospective studies on PAN and CSS. Items to be considered for analysis were collected at the time of diagnosis, during the acute phase of the disease. A survival curve was plotted for each clinical and biologic symptom observed in PAN or CSS. Each treatment arm of the prospective therapeutic trials was also tested: 1) prednisone (CS) + oral cyclophosphamide (CYC) + plasma exchanges (PE) versus CS E, 2) CS + PE versus CS, 3) CS + oral CY versus CS + pulse CY, 4) CS + pulse CY + PE versus CS + pulse CY in severe PAN and CSS, and 5) PE + antiviral agents after short-term CS in hepatitis B virus-related PAN. Of the parameters thus evaluated, the following had significant prognostic value and were responsible for higher mortality: proteinuria > 1 g/d (p < 0.0001; relative risk [RR] 3.6), renal insufficiency with serum creatinine > 1.58 mg/DL (p < 0.02; RR 1.86), GI tract involvement (p < 0.008. RR 2.83 for surgery). Cardiomyopathy and CNS involvement were associated with a RR of mortality of 2.18 and 1.76, respectively; these were not statistically significant. Similar survival rates were obtained with the prospectively tested therapies. The five-factors score (FFS) we established considered the prognostic factors creatinemia, proteinuria, cardiomyopathy, GI tract involvement, and CNS signs. Multivariate analysis showed that proteinuria (due to vascular or glomerular disease) and GI tract involvement were independent prognostic factors. When FFS = 0 (none of the 5 prognostic factors present), mortality at 5 years was 11.9%; when FFS = 1 (1 of the 5 factors present), mortality was 25.9% (p < 0.005); when FFS > 2 (3 or more of the 5 factors present), mortality was 45.95% (p < 0.0001 between 0 and 2, p < 0.05 between 1 and 2). We conclude that an initial assessment of PAN or CSS severity enables outcome and mortality to be predicted. The FFS is a good predictor of death and can be used to help the clinician choose the most adequate treatment. Renal and GI signs are the most serious prognostic factors.

Corticosteroids plus pulse cyclophosphamide and plasma exchanges versus corticosteroids plus pulse cyclophosphamide alone in the treatment of polyarteritis nodosa and churg‐strauss syndrome patients with factors predicting poor prognosis

To define the most effective treatment for severe polyarteritis nodosa (PAN) and Churg-Strauss syndrome (CSS) and to investigate the indication for plasma exchange treatment. We conducted a prospective, randomized, multicenter trial in which 62 patients were randomly assigned to receive either prednisone plus cyclophosphamide (intravenous bolus) (group A; n = 28) or prednisone plus cyclophosphamide (intravenous bolus) plus plasma exchanges (group B; n = 34) as first-line treatment for severe PAN or CSS. Factors predicting poor prognosis were renal symptoms, gastrointestinal tract involvement, cardiomyopathy, central nervous system involvement, weight loss > 10% of body weight, and age > 50 years old. Patients with hepatitis B virus-related PAN were not included in this study. The end point of the study was control of the disease (recovery or remission) or death. Clinical symptoms and laboratory findings did not differ significantly in the 2 groups. Initial control of the disease was similar in both groups. Relapse after initial control of the disease was observed in 7 patients (4 in group A and 3 in group B). The mean +/- SD followup period was 31.1 +/- 20 months for group A and 35.9 +/- 16.8 months for group B. At 5 years of followup, 38 patients (61.3%) were cured (16 in group A and 22 in group B), and 5 (8.1%) were in remission without treatment but had not yet completed the cure-defining period of 18 months (3 in group A and 2 in group B). Eight (12.9%) (2 in group A and 2 in group B) were considered to be in clinical remission and required a maintenance regimen of low-dose corticosteroids. Eleven patients died during the study period (7 in group A [25%], 4 in group B [11.8%]). Uncontrolled vasculitis was responsible for 4 deaths (2 in each group), and treatment side effects caused the death of 1 patient in group A. There was no significant difference between the 5-year cumulative survival rates of the 2 groups (75% and 88%, respectively). Based on our data, combined treatment with prednisone, cyclophosphamide, and plasma exchanges is not superior to treatment with prednisone and cyclophosphamide alone, and plasma exchanges should not be systematically proposed for initial treatment of severe PAN or CSS.